Sustained in situ protein production and release in the mammalian gut by an engineered bacteriophage

<!DOCTYPE html> <html lang="en" class="grade-c"> <head> <title>Sustained in situ protein production and release in the mammalian gut by an engineered bacteriophage | Nature Biotechnology</title> <link rel="alternate" type="application/rss+xml" href="https://www.nature.com/nbt.rss"/> <script id="save-data-connection-testing"> function hasConnection() { return navigator.connection || navigator.mozConnection || navigator.webkitConnection || navigator.msConnection; } function createLink(src) { var preloadLink = document.createElement("link"); preloadLink.rel = "preload"; preloadLink.href = src; preloadLink.as = "font"; preloadLink.type = "font/woff2"; preloadLink.crossOrigin = ""; document.head.insertBefore(preloadLink, document.head.firstChild); } var connectionDetail = { saveDataEnabled: false, slowConnection: false }; var connection = hasConnection(); if (connection) { connectionDetail.saveDataEnabled = connection.saveData; if (/\slow-2g|2g/.test(connection.effectiveType)) { connectionDetail.slowConnection = true; } } if (!(connectionDetail.saveDataEnabled || connectionDetail.slowConnection)) { createLink("/static/fonts/HardingText-Regular-Web-cecd90984f.woff2"); } else { document.documentElement.classList.add('save-data'); } </script> <link rel="preconnect" href="https://cmp.nature.com" crossorigin> <meta http-equiv="X-UA-Compatible" content="IE=edge"> <meta name="applicable-device" content="pc,mobile"> <meta name="viewport" content="width=device-width,initial-scale=1.0,maximum-scale=5,user-scalable=yes"> <meta name="360-site-verification" content="5a2dc4ab3fcb9b0393241ffbbb490480" /> <script data-test="dataLayer"> window.dataLayer = [{"content":{"category":{"contentType":"article","legacy":{"webtrendsPrimaryArticleType":"research","webtrendsSubjectTerms":"applied-microbiology;bacteriophages;biotechnology","webtrendsContentCategory":null,"webtrendsContentCollection":null,"webtrendsContentGroup":"Nature Biotechnology","webtrendsContentGroupType":null,"webtrendsContentSubGroup":"Article","status":null}},"article":{"doi":"10.1038/s41587-025-02570-7"},"attributes":{"cms":null,"deliveryPlatform":"oscar","copyright":{"open":false,"legacy":{"webtrendsLicenceType":null}}},"contentInfo":{"authors":["Zachary R. Baker","Yao Zhang","Haiyan Zhang","Hollyn C. Franklin","Priscila B. S. Serpa","Teresa Southard","Liwu Li","Bryan B. Hsu"],"publishedAt":1739836800,"publishedAtString":"2025-02-18","title":"Sustained in situ protein production and release in the mammalian gut by an engineered bacteriophage","legacy":null,"publishedAtTime":null,"documentType":"aplusplus","subjects":"Applied microbiology,Bacteriophages,Biotechnology"},"journal":{"pcode":"nbt","title":"nature biotechnology","volume":null,"issue":null,"id":41587,"publishingModel":"Hybrid Access"},"authorization":{"status":false},"features":[{"name":"furtherReadingSection","present":true}],"collection":null},"page":{"category":{"pageType":"article"},"attributes":{"template":"mosaic","featureFlags":[{"name":"nature-onwards-journey","active":false}],"testGroup":null},"search":null},"privacy":{},"version":"1.0.0","product":null,"session":null,"user":null,"backHalfContent":true,"country":"SG","hasBody":true,"uneditedManuscript":false,"twitterId":["o3xnx","o43y9","o3ef7"],"baiduId":"d38bce82bcb44717ccc29a90c4b781ea","japan":false}]; window.dataLayer.push({ ga4MeasurementId: 'G-ERRNTNZ807', ga360TrackingId: 'UA-71668177-1', twitterId: ['3xnx', 'o43y9', 'o3ef7'], baiduId: 'd38bce82bcb44717ccc29a90c4b781ea', ga4ServerUrl: 'https://collect.nature.com', imprint: 'nature' }); </script> <script> (function(w, d) { w.config = w.config || {}; w.config.mustardcut = false; if (w.matchMedia && w.matchMedia('only print, only all and (prefers-color-scheme: no-preference), only all and (prefers-color-scheme: light), only all and (prefers-color-scheme: dark)').matches) { w.config.mustardcut = true; d.classList.add('js'); d.classList.remove('grade-c'); d.classList.remove('no-js'); } })(window, document.documentElement); </script> <style>@media only print, only all and (prefers-color-scheme: no-preference), only all and (prefers-color-scheme: light), only all and (prefers-color-scheme: dark) { .c-article-editorial-summary__container .c-article-editorial-summary__article-title,.c-card--major .c-card__title,.c-card__title,.u-h2,.u-h3,h2,h3{-webkit-font-smoothing:antialiased;font-family:Harding,Palatino,serif;font-weight:700;letter-spacing:-.0117156rem}.c-article-editorial-summary__container .c-article-editorial-summary__article-title,.c-card__title,.u-h3,h3{font-size:1.25rem;line-height:1.4rem}.c-reading-companion__figure-title,.u-h4,h4{-webkit-font-smoothing:antialiased;font-weight:700;line-height:1.4rem}html{text-size-adjust:100%;box-sizing:border-box;font-size:100%;height:100%;line-height:1.15;overflow-y:scroll}body{background:#eee;color:#222;font-family:-apple-system,BlinkMacSystemFont,Segoe UI,Roboto,Oxygen-Sans,Ubuntu,Cantarell,Helvetica Neue,sans-serif;font-size:1.125rem;line-height:1.76;margin:0;min-height:100%}details,main{display:block}h1{font-size:2em;margin:.67em 0}a,sup{vertical-align:baseline}a{background-color:transparent;color:#069;overflow-wrap:break-word;text-decoration:underline;text-decoration-skip-ink:auto;word-break:break-word}b{font-weight:bolder}sup{font-size:75%;line-height:0;position:relative;top:-.5em}img{border:0;height:auto;max-width:100%;vertical-align:middle}button,input,select{font-family:inherit;font-size:100%;line-height:1.15;margin:0}button,input{overflow:visible}button,select{text-transform:none}[type=submit],button{-webkit-appearance:button}[type=checkbox]{box-sizing:border-box;padding:0}summary{display:list-item}[hidden]{display:none}button{border-radius:0;cursor:pointer;font-family:-apple-system,BlinkMacSystemFont,Segoe UI,Roboto,Oxygen-Sans,Ubuntu,Cantarell,Helvetica Neue,sans-serif}h1{-webkit-font-smoothing:antialiased;font-family:Harding,Palatino,serif;font-size:2rem;font-weight:700;letter-spacing:-.0390625rem;line-height:2.25rem}.c-card--major .c-card__title,.u-h2,.u-h3,h2{font-family:Harding,Palatino,serif;letter-spacing:-.0117156rem}.c-card--major .c-card__title,.u-h2,h2{-webkit-font-smoothing:antialiased;font-size:1.5rem;font-weight:700;line-height:1.6rem}.u-h3{font-size:1.25rem}.c-card__title,.c-reading-companion__figure-title,.u-h3,.u-h4,h4,h5,h6{-webkit-font-smoothing:antialiased;font-weight:700;line-height:1.4rem}.c-article-editorial-summary__container .c-article-editorial-summary__article-title,.c-card__title,h3{font-family:Harding,Palatino,serif;font-size:1.25rem}.c-article-editorial-summary__container .c-article-editorial-summary__article-title,h3{-webkit-font-smoothing:antialiased;font-weight:700;letter-spacing:-.0117156rem;line-height:1.4rem}.c-reading-companion__figure-title,.u-h4,h4{font-family:-apple-system,BlinkMacSystemFont,Segoe UI,Roboto,Oxygen-Sans,Ubuntu,Cantarell,Helvetica Neue,sans-serif;font-size:1.125rem;letter-spacing:-.0117156rem}button:focus{outline:3px solid #fece3e;will-change:transform}input+label{padding-left:.5em}nav ol,nav ul{list-style:none none}p:empty{display:none}.sans-serif{font-family:-apple-system,BlinkMacSystemFont,Segoe UI,Roboto,Oxygen-Sans,Ubuntu,Cantarell,Helvetica Neue,sans-serif}.article-page{background:#fff}.c-article-header{font-family:-apple-system,BlinkMacSystemFont,Segoe UI,Roboto,Oxygen-Sans,Ubuntu,Cantarell,Helvetica Neue,sans-serif;margin-bottom:40px}.c-article-identifiers{color:#6f6f6f;display:flex;flex-wrap:wrap;font-size:1rem;line-height:1.3;list-style:none;margin:0 0 8px;padding:0}.c-article-identifiers__item{border-right:1px solid #6f6f6f;list-style:none;margin-right:8px;padding-right:8px}.c-article-identifiers__item:last-child{border-right:0;margin-right:0;padding-right:0}.c-article-title{font-size:1.5rem;line-height:1.25;margin:0 0 16px}@media only screen and (min-width:768px){.c-article-title{font-size:1.875rem;line-height:1.2}}.c-article-author-list{display:inline;font-size:1rem;list-style:none;margin:0 8px 0 0;padding:0;width:100%}.c-article-author-list__item{display:inline;padding-right:0}.c-article-author-list svg{margin-left:4px}.c-article-author-list__show-more{display:none;margin-right:4px}.c-article-author-list__button,.js .c-article-author-list__item--hide,.js .c-article-author-list__show-more{display:none}.js .c-article-author-list--long .c-article-author-list__show-more,.js .c-article-author-list--long+.c-article-author-list__button{display:inline}@media only screen and (max-width:539px){.js .c-article-author-list__item--hide-small-screen{display:none}.js .c-article-author-list--short .c-article-author-list__show-more,.js .c-article-author-list--short+.c-article-author-list__button{display:inline}}#uptodate-client,.js .c-article-author-list--expanded .c-article-author-list__show-more{display:none!important}.js .c-article-author-list--expanded .c-article-author-list__item--hide-small-screen{display:inline!important}.c-article-author-list__button,.c-button-author-list{background:#ebf1f5;border:4px solid #ebf1f5;border-radius:20px;color:#666;font-size:.875rem;line-height:1.4;padding:2px 11px 2px 8px;text-decoration:none}.c-article-author-list__button svg,.c-button-author-list svg{margin:1px 4px 0 0}.c-article-author-list__button:hover,.c-button-author-list:hover{background:#069;border-color:transparent;color:#fff}.c-article-info-details{font-size:1rem;margin-bottom:8px;margin-top:16px}.c-article-info-details__cite-as{border-left:1px solid #6f6f6f;margin-left:8px;padding-left:8px}.c-article-metrics-bar{display:flex;flex-wrap:wrap;font-size:1rem;line-height:1.3}.c-article-metrics-bar__wrapper{margin:16px 0}.c-article-metrics-bar__item{align-items:baseline;border-right:1px solid #6f6f6f;margin-right:8px}.c-article-metrics-bar__item:last-child{border-right:0}.c-article-metrics-bar__count{font-weight:700;margin:0}.c-article-metrics-bar__label{color:#626262;font-style:normal;font-weight:400;margin:0 10px 0 5px}.c-article-metrics-bar__details{margin:0}.c-article-main-column{font-family:Harding,Palatino,serif;margin-right:8.6%;width:60.2%}@media only screen and (max-width:1023px){.c-article-main-column{margin-right:0;width:100%}}.c-article-extras{float:left;font-family:-apple-system,BlinkMacSystemFont,Segoe UI,Roboto,Oxygen-Sans,Ubuntu,Cantarell,Helvetica Neue,sans-serif;width:31.2%}@media only screen and (max-width:1023px){.c-article-extras{display:none}}.c-article-associated-content__container .c-article-associated-content__title,.c-article-section__title{border-bottom:2px solid #d5d5d5;font-size:1.25rem;margin:0;padding-bottom:8px}@media only screen and (min-width:768px){.c-article-associated-content__container .c-article-associated-content__title,.c-article-section__title{font-size:1.5rem;line-height:1.24}}.c-article-associated-content__container .c-article-associated-content__title{margin-bottom:8px}.c-article-body p{margin-bottom:24px;margin-top:0}.c-article-section{clear:both}.c-article-section__content{margin-bottom:40px;padding-top:8px}@media only screen and (max-width:1023px){.c-article-section__content{padding-left:0}}.c-article-authors-search{margin-bottom:24px;margin-top:0}.c-article-authors-search__item,.c-article-authors-search__title{font-family:-apple-system,BlinkMacSystemFont,Segoe UI,Roboto,Oxygen-Sans,Ubuntu,Cantarell,Helvetica Neue,sans-serif}.c-article-authors-search__title{color:#626262;font-size:1.05rem;font-weight:700;margin:0;padding:0}.c-article-authors-search__item{font-size:1rem}.c-article-authors-search__text{margin:0}.c-article-license__badge,c-card__section{margin-top:8px}.c-code-block{border:1px solid #eee;font-family:monospace;margin:0 0 24px;padding:20px}.c-code-block__heading{font-weight:400;margin-bottom:16px}.c-code-block__line{display:block;overflow-wrap:break-word;white-space:pre-wrap}.c-article-share-box__no-sharelink-info{font-size:.813rem;font-weight:700;margin-bottom:24px;padding-top:4px}.c-article-share-box__only-read-input{border:1px solid #d5d5d5;box-sizing:content-box;display:inline-block;font-size:.875rem;font-weight:700;height:24px;margin-bottom:8px;padding:8px 10px}.c-article-share-box__button--link-like{background-color:transparent;border:0;color:#069;cursor:pointer;font-size:.875rem;margin-bottom:8px;margin-left:10px}.c-article-editorial-summary__container{font-family:-apple-system,BlinkMacSystemFont,Segoe UI,Roboto,Oxygen-Sans,Ubuntu,Cantarell,Helvetica Neue,sans-serif;font-size:1rem}.c-article-editorial-summary__container .c-article-editorial-summary__content p:last-child{margin-bottom:0}.c-article-editorial-summary__container .c-article-editorial-summary__content--less{max-height:9.5rem;overflow:hidden}.c-article-editorial-summary__container .c-article-editorial-summary__button{background-color:#fff;border:0;color:#069;font-size:.875rem;margin-bottom:16px}.c-article-editorial-summary__container .c-article-editorial-summary__button.active,.c-article-editorial-summary__container .c-article-editorial-summary__button.hover,.c-article-editorial-summary__container .c-article-editorial-summary__button:active,.c-article-editorial-summary__container .c-article-editorial-summary__button:hover{text-decoration:underline;text-decoration-skip-ink:auto}.c-article-associated-content__container .c-article-associated-content__collection-label{font-size:.875rem;line-height:1.4}.c-article-associated-content__container .c-article-associated-content__collection-title{line-height:1.3}.c-context-bar{box-shadow:0 0 10px 0 rgba(51,51,51,.2);position:relative;width:100%}.c-context-bar__title{display:none}.c-reading-companion{clear:both;min-height:389px}.c-reading-companion__sticky{max-width:389px}.c-reading-companion__scroll-pane{margin:0;min-height:200px;overflow:hidden auto}.c-reading-companion__tabs{display:flex;flex-flow:row nowrap;font-size:1rem;list-style:none;margin:0 0 8px;padding:0}.c-reading-companion__tabs>li{flex-grow:1}.c-reading-companion__tab{background-color:#eee;border:1px solid #d5d5d5;border-image:initial;border-left-width:0;color:#069;font-size:1rem;padding:8px 8px 8px 15px;text-align:left;width:100%}.c-reading-companion__tabs li:first-child .c-reading-companion__tab{border-left-width:1px}.c-reading-companion__tab--active{background-color:#fff;border-bottom:1px solid #fff;color:#222;font-weight:700}.c-reading-companion__sections-list{list-style:none;padding:0}.c-reading-companion__figures-list,.c-reading-companion__references-list{list-style:none;min-height:389px;padding:0}.c-reading-companion__references-list--numeric{list-style:decimal inside}.c-reading-companion__sections-list{margin:0 0 8px;min-height:50px}.c-reading-companion__section-item{font-size:1rem;padding:0}.c-reading-companion__section-item a{display:block;line-height:1.5;overflow:hidden;padding:8px 0 8px 16px;text-overflow:ellipsis;white-space:nowrap}.c-reading-companion__figure-item{border-top:1px solid #d5d5d5;font-size:1rem;padding:16px 8px 16px 0}.c-reading-companion__figure-item:first-child{border-top:none;padding-top:8px}.c-reading-companion__reference-item{border-top:1px solid #d5d5d5;font-size:1rem;padding:8px 8px 8px 16px}.c-reading-companion__reference-item:first-child{border-top:none}.c-reading-companion__reference-item a{word-break:break-word}.c-reading-companion__reference-citation{display:inline}.c-reading-companion__reference-links{font-size:.813rem;font-weight:700;list-style:none;margin:8px 0 0;padding:0;text-align:right}.c-reading-companion__reference-links>a{display:inline-block;padding-left:8px}.c-reading-companion__reference-links>a:first-child{display:inline-block;padding-left:0}.c-reading-companion__figure-title{display:block;margin:0 0 8px}.c-reading-companion__figure-links{display:flex;justify-content:space-between;margin:8px 0 0}.c-reading-companion__figure-links>a{align-items:center;display:flex}.c-reading-companion__figure-full-link svg{height:.8em;margin-left:2px}.c-reading-companion__panel{border-top:none;display:none;margin-top:0;padding-top:0}.c-cod,.c-reading-companion__panel--active{display:block}.c-cod{font-size:1rem;width:100%}.c-cod__form{background:#ebf0f3}.c-cod__prompt{font-size:1.125rem;line-height:1.3;margin:0 0 24px}.c-cod__label{display:block;margin:0 0 4px}.c-cod__row{display:flex;margin:0 0 16px}.c-cod__row:last-child{margin:0}.c-cod__input{border:1px solid #d5d5d5;border-radius:2px;flex-basis:75%;flex-shrink:0;margin:0;padding:13px}.c-cod__input--submit{background-color:#069;border:1px solid #069;color:#fff;flex-shrink:1;margin-left:8px;transition:background-color .2s ease-out 0s,color .2s ease-out 0s}.c-cod__input--submit-single{flex-basis:100%;flex-shrink:0;margin:0}.c-cod__input--submit:focus,.c-cod__input--submit:hover{background-color:#fff;color:#069}.c-pdf-download__link .u-icon{padding-top:2px}.c-pdf-download{display:flex;margin-bottom:16px;max-height:48px}@media only screen and (min-width:540px){.c-pdf-download{max-height:none}}@media only screen and (min-width:1024px){.c-pdf-download{max-height:48px}}.c-pdf-download__link{display:flex;flex:1 1 0%}.c-pdf-download__link:hover{text-decoration:none}.c-pdf-download__text{padding-right:4px}@media only screen and (max-width:539px){.c-pdf-download__text{text-transform:capitalize}}@media only screen and (min-width:540px){.c-pdf-download__text{padding-right:8px}}.c-context-bar--sticky .c-pdf-download{display:block;margin-bottom:0;white-space:nowrap}@media only screen and (max-width:539px){.c-pdf-download .u-sticky-visually-hidden{clip:rect(0,0,0,0);border:0;height:1px;margin:-100%;overflow:hidden;padding:0;position:absolute!important;width:1px}}.c-pdf-container{display:flex;justify-content:flex-end}@media only screen and (max-width:539px){.c-pdf-container .c-pdf-download{display:flex;flex-basis:100%}}.c-pdf-container .c-pdf-download+.c-pdf-download{margin-left:16px}.c-article-extras .c-pdf-container .c-pdf-download{width:100%}.c-article-extras .c-pdf-container .c-pdf-download+.c-pdf-download{margin-left:0}@media only screen and (min-width:540px){.c-context-bar--sticky .c-pdf-download__link{align-items:center;flex:1 1 183px}}@media only screen and (max-width:320px){.c-context-bar--sticky .c-pdf-download__link{padding:16px}}.article-page--commercial .c-article-main-column .c-pdf-button__container .c-pdf-download{display:none}@media only screen and (max-width:1023px){.article-page--commercial .c-article-main-column .c-pdf-button__container .c-pdf-download{display:block}}.c-status-message--success{border-bottom:2px solid #00b8b0;justify-content:center;margin-bottom:16px;padding-bottom:8px}.c-recommendations-list__item .c-card{flex-basis:100%}.c-recommendations-list__item .c-card__image{align-items:baseline;flex:1 1 40%;margin:0 0 0 16px;max-width:150px}.c-recommendations-list__item .c-card__image img{border:1px solid #cedbe0;height:auto;min-height:0;position:static}@media only screen and (max-width:1023px){.c-recommendations-list__item .c-card__image{display:none}}.c-card__layout{display:flex;flex:1 1 auto;justify-content:space-between}.c-card__title-recommendation{-webkit-box-orient:vertical;-webkit-line-clamp:4;display:-webkit-box;font-size:1rem;font-weight:700;line-height:1.4;margin:0 0 8px;max-height:5.6em;overflow:hidden!important;text-overflow:ellipsis}.c-card__title-recommendation .c-card__link{color:inherit}.c-card__title-recommendation .c-card__link:hover{text-decoration:underline}.c-card__title-recommendation .MathJax_Display{display:inline!important}.c-card__link:not(.c-card__link--no-block-link):before{z-index:1}.c-article-metrics__heading a,.c-article-metrics__posts .c-card__title a,.c-article-recommendations-card__link{color:inherit}.c-recommendations-column-switch .c-meta{margin-top:auto}.c-article-recommendations-card__meta-type,.c-meta .c-meta__item:first-child{font-weight:700}.c-article-body .c-article-recommendations-card__authors{display:none;font-family:-apple-system,BlinkMacSystemFont,Segoe UI,Roboto,Oxygen-Sans,Ubuntu,Cantarell,Helvetica Neue,sans-serif;font-size:.875rem;line-height:1.5;margin:0 0 8px}@media only screen and (max-width:539px){.c-article-body .c-article-recommendations-card__authors{display:block;margin:0}}.c-article-metrics__posts .c-card__title{font-size:1.05rem}.c-article-metrics__posts .c-card__title+span{color:#6f6f6f;font-size:1rem}p{overflow-wrap:break-word;word-break:break-word}.c-ad{text-align:center}@media only screen and (min-width:320px){.c-ad{padding:8px}}.c-ad--728x90{background-color:#ccc;display:none}.c-ad--728x90 .c-ad__inner{min-height:calc(1.5em + 94px)}@media only screen and (min-width:768px){.js .c-ad--728x90{display:none}}.c-ad__label{color:#333;font-family:-apple-system,BlinkMacSystemFont,Segoe UI,Roboto,Oxygen-Sans,Ubuntu,Cantarell,Helvetica Neue,sans-serif;font-size:.875rem;font-weight:400;line-height:1.5;margin-bottom:4px}.c-author-list{color:#6f6f6f;font-family:inherit;font-size:1rem;line-height:inherit;list-style:none;margin:0;padding:0}.c-author-list>li,.c-breadcrumbs>li,.c-footer__links>li,.js .c-author-list,.u-list-comma-separated>li,.u-list-inline>li{display:inline}.c-author-list>li:not(:first-child):not(:last-child):before{content:", "}.c-author-list>li:not(:only-child):last-child:before{content:" & "}.c-author-list--compact{font-size:.875rem;line-height:1.4}.c-author-list--truncated>li:not(:only-child):last-child:before{content:" ... "}.js .c-author-list__hide{display:none;visibility:hidden}.js .c-author-list__hide:first-child+*{margin-block-start:0}.c-meta{color:inherit;font-family:-apple-system,BlinkMacSystemFont,Segoe UI,Roboto,Oxygen-Sans,Ubuntu,Cantarell,Helvetica Neue,sans-serif;font-size:.875rem;line-height:1.4;list-style:none;margin:0;padding:0}.c-meta--large{font-size:1rem}.c-meta--large .c-meta__item{margin-bottom:8px}.c-meta__item{display:inline-block;margin-bottom:4px}.c-meta__item:not(:last-child){border-right:1px solid #d5d5d5;margin-right:4px;padding-right:4px}@media only screen and (max-width:539px){.c-meta__item--block-sm-max{display:block}.c-meta__item--block-sm-max:not(:last-child){border-right:none;margin-right:0;padding-right:0}}@media only screen and (min-width:1024px){.c-meta__item--block-at-lg{display:block}.c-meta__item--block-at-lg:not(:last-child){border-right:none;margin-right:0;padding-right:0}}.c-meta__type{font-weight:700;text-transform:none}.c-skip-link{background:#069;bottom:auto;color:#fff;font-family:-apple-system,BlinkMacSystemFont,Segoe UI,Roboto,Oxygen-Sans,Ubuntu,Cantarell,Helvetica Neue,sans-serif;font-size:.875rem;padding:8px;position:absolute;text-align:center;transform:translateY(-100%);z-index:9999}@media (prefers-reduced-motion:reduce){.c-skip-link{transition:top .3s ease-in-out 0s}}@media print{.c-skip-link{display:none}}.c-skip-link:link{color:#fff}.c-status-message{align-items:center;box-sizing:border-box;display:flex;font-family:-apple-system,BlinkMacSystemFont,Segoe UI,Roboto,Oxygen-Sans,Ubuntu,Cantarell,Helvetica Neue,sans-serif;font-size:1rem;position:relative;width:100%}.c-card__summary>p:last-child,.c-status-message :last-child{margin-bottom:0}.c-status-message--boxed{background-color:#fff;border:1px solid #eee;border-radius:2px;line-height:1.4;padding:16px}.c-status-message__heading{font-family:-apple-system,BlinkMacSystemFont,Segoe UI,Roboto,Oxygen-Sans,Ubuntu,Cantarell,Helvetica Neue,sans-serif;font-size:1rem;font-weight:700}.c-status-message__icon{fill:currentcolor;display:inline-block;flex:0 0 auto;height:1.5em;margin-right:8px;transform:translate(0);vertical-align:text-top;width:1.5em}.c-status-message__icon--top{align-self:flex-start}.c-status-message--info .c-status-message__icon{color:#003f8d}.c-status-message--boxed.c-status-message--info{border-bottom:4px solid #003f8d}.c-status-message--error .c-status-message__icon{color:#c40606}.c-status-message--boxed.c-status-message--error{border-bottom:4px solid #c40606}.c-status-message--success .c-status-message__icon{color:#00b8b0}.c-status-message--boxed.c-status-message--success{border-bottom:4px solid #00b8b0}.c-status-message--warning .c-status-message__icon{color:#edbc53}.c-status-message--boxed.c-status-message--warning{border-bottom:4px solid #edbc53}.c-breadcrumbs{color:#000;font-family:-apple-system,BlinkMacSystemFont,Segoe UI,Roboto,Oxygen-Sans,Ubuntu,Cantarell,Helvetica Neue,sans-serif;font-size:1rem;list-style:none;margin:0;padding:0}.c-breadcrumbs__link{color:#666}svg.c-breadcrumbs__chevron{fill:#888;height:10px;margin:4px 4px 0;width:10px}@media only screen and (max-width:539px){.c-breadcrumbs .c-breadcrumbs__item{display:none}.c-breadcrumbs .c-breadcrumbs__item:last-child,.c-breadcrumbs .c-breadcrumbs__item:nth-last-child(2){display:inline}}.c-card{background-color:transparent;border:0;box-shadow:none;display:flex;flex-direction:column;font-size:14px;min-width:0;overflow:hidden;padding:0;position:relative}.c-card--no-shape{background:0 0;border:0;box-shadow:none}.c-card__image{display:flex;justify-content:center;overflow:hidden;padding-bottom:56.25%;position:relative}@supports (aspect-ratio:1/1){.c-card__image{padding-bottom:0}}.c-card__image img{left:0;min-height:100%;min-width:100%;position:absolute}@supports ((-o-object-fit:cover) or (object-fit:cover)){.c-card__image img{height:100%;object-fit:cover;width:100%}}.c-card__body{flex:1 1 auto;padding:16px}.c-card--no-shape .c-card__body{padding:0}.c-card--no-shape .c-card__body:not(:first-child){padding-top:16px}.c-card__title{letter-spacing:-.01875rem;margin-bottom:8px;margin-top:0}[lang=de] .c-card__title{hyphens:auto}.c-card__summary{line-height:1.4}.c-card__summary>p{margin-bottom:5px}.c-card__summary a{text-decoration:underline}.c-card__link:not(.c-card__link--no-block-link):before{bottom:0;content:"";left:0;position:absolute;right:0;top:0}.c-card--flush .c-card__body{padding:0}.c-card--major{font-size:1rem}.c-card--dark{background-color:#29303c;border-width:0;color:#e3e4e5}.c-card--dark .c-card__title{color:#fff}.c-card--dark .c-card__link,.c-card--dark .c-card__summary a{color:inherit}.c-header{background-color:#fff;border-bottom:5px solid #000;font-size:1rem;line-height:1.4;margin-bottom:16px}.c-header__row{padding:0;position:relative}.c-header__row:not(:last-child){border-bottom:1px solid #eee}.c-header__split{align-items:center;display:flex;justify-content:space-between}.c-header__logo-container{flex:1 1 0px;line-height:0;margin:8px 24px 8px 0}.c-header__logo{transform:translateZ(0)}.c-header__logo img{max-height:32px}.c-header__container{margin:0 auto;max-width:1280px}.c-header__menu{align-items:center;display:flex;flex:0 1 auto;flex-wrap:wrap;font-weight:700;gap:8px 8px;line-height:1.4;list-style:none;margin:0 -8px;padding:0}@media print{.c-header__menu{display:none}}@media only screen and (max-width:1023px){.c-header__menu--hide-lg-max{display:none;visibility:hidden}}.c-header__menu--global{font-weight:400;justify-content:flex-end}.c-header__menu--global svg{display:none;visibility:hidden}.c-header__menu--global svg:first-child+*{margin-block-start:0}@media only screen and (min-width:540px){.c-header__menu--global svg{display:block;visibility:visible}}.c-header__menu--journal{font-size:.875rem;margin:8px 0 8px -8px}@media only screen and (min-width:540px){.c-header__menu--journal{flex-wrap:nowrap;font-size:1rem}}.c-header__item{padding-bottom:0;padding-top:0;position:static}.c-header__item--pipe{border-left:2px solid #eee;padding-left:8px}.c-header__item--padding{padding-bottom:8px;padding-top:8px}@media only screen and (min-width:540px){.c-header__item--dropdown-menu{position:relative}}@media only screen and (min-width:1024px){.c-header__item--hide-lg{display:none;visibility:hidden}}@media only screen and (max-width:767px){.c-header__item--hide-md-max{display:none;visibility:hidden}.c-header__item--hide-md-max:first-child+*{margin-block-start:0}}.c-header__link{align-items:center;color:inherit;display:inline-flex;gap:4px 4px;padding:8px;white-space:nowrap}.c-header__link svg{transition-duration:.2s}.c-header__show-text{display:none;visibility:hidden}.has-tethered .c-header__heading--js-hide:first-child+*{margin-block-start:0}@media only screen and (min-width:540px){.c-header__show-text{display:inline;visibility:visible}}.c-header__dropdown{background-color:#000;border-bottom:1px solid #2f2f2f;color:#eee;font-size:.875rem;line-height:1.2;padding:16px 0}@media print{.c-header__dropdown{display:none}}.c-header__heading{display:inline-block;font-family:-apple-system,BlinkMacSystemFont,Segoe UI,Roboto,Oxygen-Sans,Ubuntu,Cantarell,Helvetica Neue,sans-serif;font-size:1.25rem;font-weight:400;line-height:1.4;margin-bottom:8px}.c-header__heading--keyline{border-top:1px solid;border-color:#2f2f2f;margin-top:16px;padding-top:16px;width:100%}.c-header__list{display:flex;flex-wrap:wrap;gap:0 16px;list-style:none;margin:0 -8px}.c-header__flush{margin:0 -8px}.c-header__visually-hidden{clip:rect(0,0,0,0);border:0;height:1px;margin:-100%;overflow:hidden;padding:0;position:absolute!important;width:1px}.c-header__search-form{margin-bottom:8px}.c-header__search-layout{display:flex;flex-wrap:wrap;gap:16px 16px}.c-header__search-layout>:first-child{flex:999 1 auto}.c-header__search-layout>*{flex:1 1 auto}.c-header__search-layout--max-width{max-width:720px}.c-header__search-button{align-items:center;background-color:transparent;background-image:none;border:1px solid #fff;border-radius:2px;color:#fff;cursor:pointer;display:flex;font-family:sans-serif;font-size:1rem;justify-content:center;line-height:1.15;margin:0;padding:8px 16px;position:relative;text-decoration:none;transition:all .25s ease 0s,color .25s ease 0s,border-color .25s ease 0s;width:100%}.u-button svg,.u-button--primary svg{fill:currentcolor}.c-header__input,.c-header__select{border:1px solid;border-radius:3px;box-sizing:border-box;font-size:1rem;padding:8px 16px;width:100%}.c-header__select{-webkit-appearance:none;background-image:url("data:image/svg+xml,%3Csvg height='16' viewBox='0 0 16 16' width='16' xmlns='http://www.w3.org/2000/svg'%3E%3Cpath d='m5.58578644 3-3.29289322-3.29289322c-.39052429-.39052429-.39052429-1.02368927 0-1.41421356s1.02368927-.39052429 1.41421356 0l4 4c.39052429.39052429.39052429 1.02368927 0 1.41421356l-4 4c-.39052429.39052429-1.02368927.39052429-1.41421356 0s-.39052429-1.02368927 0-1.41421356z' fill='%23333' fill-rule='evenodd' transform='matrix(0 1 -1 0 11 3)'/%3E%3C/svg%3E");background-position:right .7em top 50%;background-repeat:no-repeat;background-size:1em;box-shadow:0 1px 0 1px rgba(0,0,0,.04);display:block;margin:0;max-width:100%;min-width:150px}@media only screen and (min-width:540px){.c-header__menu--journal .c-header__item--dropdown-menu:last-child .c-header__dropdown.has-tethered{left:auto;right:0}}@media only screen and (min-width:768px){.c-header__menu--journal .c-header__item--dropdown-menu:last-child .c-header__dropdown.has-tethered{left:0;right:auto}}.c-header__dropdown.has-tethered{border-bottom:0;border-radius:0 0 2px 2px;left:0;position:absolute;top:100%;transform:translateY(5px);width:100%;z-index:1}@media only screen and (min-width:540px){.c-header__dropdown.has-tethered{transform:translateY(8px);width:auto}}@media only screen and (min-width:768px){.c-header__dropdown.has-tethered{min-width:225px}}.c-header__dropdown--full-width.has-tethered{padding:32px 0 24px;transform:none;width:100%}.has-tethered .c-header__heading--js-hide{display:none;visibility:hidden}.has-tethered .c-header__list--js-stack{flex-direction:column}.has-tethered .c-header__item--keyline,.has-tethered .c-header__list~.c-header__list .c-header__item:first-child{border-top:1px solid #d5d5d5;margin-top:8px;padding-top:8px}.c-header__item--snid-account-widget{display:flex}.c-header__container{padding:0 4px}.c-header__list{padding:0 12px}.c-header__menu .c-header__link{font-size:14px}.c-header__item--snid-account-widget .c-header__link{padding:8px}.c-header__menu--journal{margin-left:0}@media only screen and (min-width:540px){.c-header__container{padding:0 16px}.c-header__menu--journal{margin-left:-8px}.c-header__menu .c-header__link{font-size:16px}.c-header__link--search{gap:13px 13px}}.u-button{align-items:center;background-color:transparent;background-image:none;border:1px solid #069;border-radius:2px;color:#069;cursor:pointer;display:inline-flex;font-family:sans-serif;font-size:1rem;justify-content:center;line-height:1.3;margin:0;padding:8px;position:relative;text-decoration:none;transition:all .25s ease 0s,color .25s ease 0s,border-color .25s ease 0s;width:auto}.u-button--primary{background-color:#069;background-image:none;border:1px solid #069;color:#fff}.u-button--full-width{display:flex;width:100%}.u-display-none{display:none}.js .u-js-hide,.u-hide{display:none;visibility:hidden}.u-hide:first-child+*{margin-block-start:0}.u-visually-hidden{clip:rect(0,0,0,0);border:0;height:1px;margin:-100%;overflow:hidden;padding:0;position:absolute!important;width:1px}@media print{.u-hide-print{display:none}}@media only screen and (min-width:1024px){.u-hide-at-lg{display:none;visibility:hidden}.u-hide-at-lg:first-child+*{margin-block-start:0}}.u-clearfix:after,.u-clearfix:before{content:"";display:table}.u-clearfix:after{clear:both}.u-color-open-access{color:#b74616}.u-float-left{float:left}.u-icon{fill:currentcolor;display:inline-block;height:1em;transform:translate(0);vertical-align:text-top;width:1em}.u-full-height{height:100%}.u-list-reset{list-style:none;margin:0;padding:0}.u-sans-serif{font-family:-apple-system,BlinkMacSystemFont,Segoe UI,Roboto,Oxygen-Sans,Ubuntu,Cantarell,Helvetica Neue,sans-serif}.u-container{margin:0 auto;max-width:1280px;padding:0 16px}.u-justify-content-space-between{justify-content:space-between}.u-mt-32{margin-top:32px}.u-mb-8{margin-bottom:8px}.u-mb-16{margin-bottom:16px}.u-mb-24{margin-bottom:24px}.u-mb-32{margin-bottom:32px}.c-nature-box svg+.c-article__button-text,.u-ml-8{margin-left:8px}.u-pa-16{padding:16px}html *,html :after,html :before{box-sizing:inherit}.c-article-section__title,.c-article-title{font-weight:700}.c-card__title{line-height:1.4em}.c-article__button{background-color:#069;border:1px solid #069;border-radius:2px;color:#fff;display:flex;font-family:-apple-system,BlinkMacSystemFont,Segoe UI,Roboto,Oxygen-Sans,Ubuntu,Cantarell,Helvetica Neue,sans-serif;font-size:.875rem;line-height:1.4;margin-bottom:16px;padding:13px;transition:background-color .2s ease-out 0s,color .2s ease-out 0s}.c-article__button,.c-article__button:hover{text-decoration:none}.c-article__button--inverted,.c-article__button:hover{background-color:#fff;color:#069}.c-article__button--inverted:hover{background-color:#069;color:#fff}.c-header__link{text-decoration:inherit}.grade-c-hide{display:block}.u-lazy-ad-wrapper{background-color:#ccc;display:none;min-height:137px}@media only screen and (min-width:768px){.u-lazy-ad-wrapper{display:block}}.c-nature-box{background-color:#fff;border:1px solid #d5d5d5;border-radius:2px;box-shadow:0 0 5px 0 rgba(51,51,51,.1);line-height:1.3;margin-bottom:24px;padding:16px 16px 3px}.c-nature-box__text{font-size:1rem;margin-bottom:16px}.c-nature-box .c-pdf-download{margin-bottom:16px!important}.c-nature-box--version{background-color:#eee}.c-nature-box__wrapper{transform:translateZ(0)}.c-nature-box__wrapper--placeholder{min-height:165px}.c-pdf-download__link{padding:13px 24px} } </style> <link data-test="critical-css-handler" data-inline-css-source="critical-css" rel="stylesheet" href="/static/css/enhanced-article-nature-branded-d54f9178e8.css" media="print" onload="this.media='only print, only all and (prefers-color-scheme: no-preference), only all and (prefers-color-scheme: light), only all and (prefers-color-scheme: dark)';this.onload=null"> <noscript> <link rel="stylesheet" type="text/css" href="/static/css/enhanced-article-nature-branded-d54f9178e8.css" media="only print, only all and (prefers-color-scheme: no-preference), only all and (prefers-color-scheme: light), only all and (prefers-color-scheme: dark)"> </noscript> <link rel="stylesheet" type="text/css" href="/static/css/article-print-122346e276.css" media="print"> <link rel="apple-touch-icon" sizes="180x180" href=/static/images/favicons/nature/apple-touch-icon-f39cb19454.png> <link rel="icon" type="image/png" sizes="48x48" href=/static/images/favicons/nature/favicon-48x48-b52890008c.png> <link rel="icon" type="image/png" sizes="32x32" href=/static/images/favicons/nature/favicon-32x32-3fe59ece92.png> <link rel="icon" type="image/png" sizes="16x16" href=/static/images/favicons/nature/favicon-16x16-951651ab72.png> <link rel="manifest" href=/static/manifest.json crossorigin="use-credentials"> <link rel="mask-icon" href=/static/images/favicons/nature/safari-pinned-tab-69bff48fe6.svg color="#000000"> <link rel="shortcut icon" href=/static/images/favicons/nature/favicon.ico> <meta name="msapplication-TileColor" content="#000000"> <meta name="msapplication-config" content=/static/browserconfig.xml> <meta name="theme-color" content="#000000"> <meta name="application-name" content="Nature"> <script> (function () { if ( typeof window.CustomEvent === "function" ) return false; function CustomEvent ( event, params ) { params = params || { bubbles: false, cancelable: false, detail: null }; var evt = document.createEvent( 'CustomEvent' ); evt.initCustomEvent( event, params.bubbles, params.cancelable, params.detail ); return evt; } CustomEvent.prototype = window.Event.prototype; window.CustomEvent = CustomEvent; })(); </script>  <script data-test="gtm-head"> window.initGTM = function() { if (window.config.mustardcut) { (function (w, d, s, l, i) { w[l] = w[l] || []; w[l].push({'gtm.start': new Date().getTime(), event: 'gtm.js'}); var f = d.getElementsByTagName(s)[0], j = d.createElement(s), dl = l != 'dataLayer' ? '&l=' + l : ''; j.async = true; j.src = 'https://www.googletagmanager.com/gtm.js?id=' + i + dl; f.parentNode.insertBefore(j, f); })(window, document, 'script', 'dataLayer', 'GTM-MRVXSHQ'); } } </script>  <script> (function(w,d,t) { function cc() { var h = w.location.hostname; if (h.indexOf('preview-www.nature.com') > -1) return; var e = d.createElement(t), s = d.getElementsByTagName(t)[0]; if (h.indexOf('nature.com') > -1) { if (h.indexOf('test-www.nature.com') > -1) { e.src = 'https://cmp.nature.com/production_live/en/consent-bundle-8-74.js'; e.setAttribute('onload', "initGTM(window,document,'script','dataLayer','GTM-MRVXSHQ')"); } else { e.src = 'https://cmp.nature.com/production_live/en/consent-bundle-8-74.js'; e.setAttribute('onload', "initGTM(window,document,'script','dataLayer','GTM-MRVXSHQ')"); } } else { e.src = '/static/js/cookie-consent-es5-bundle-cb57c2c98a.js'; e.setAttribute('data-consent', h); } s.insertAdjacentElement('afterend', e); } cc(); })(window,document,'script'); </script> <script id="js-position0"> (function(w, d) { w.idpVerifyPrefix = 'https://verify.nature.com'; w.ra21Host = 'https://wayf.springernature.com'; var moduleSupport = (function() { return 'noModule' in d.createElement('script'); })(); if (w.config.mustardcut === true) { w.loader = { index: 0, registered: [], scripts: [ {src: '/static/js/global-article-es6-bundle-c8a573ca90.js', test: 'global-article-js', module: true}, {src: '/static/js/global-article-es5-bundle-d17603b9e9.js', test: 'global-article-js', nomodule: true}, {src: '/static/js/shared-es6-bundle-606cb67187.js', test: 'shared-js', module: true}, {src: '/static/js/shared-es5-bundle-e919764a53.js', test: 'shared-js', nomodule: true}, {src: '/static/js/header-150-es6-bundle-5bb959eaa1.js', test: 'header-150-js', module: true}, {src: '/static/js/header-150-es5-bundle-994fde5b1d.js', test: 'header-150-js', nomodule: true} ].filter(function (s) { if (s.src === null) return false; if (moduleSupport && s.nomodule) return false; return !(!moduleSupport && s.module); }), register: function (value) { this.registered.push(value); }, ready: function () { if (this.registered.length === this.scripts.length) { this.registered.forEach(function (fn) { if (typeof fn === 'function') { setTimeout(fn, 0); } }); this.ready = function () {}; } }, insert: function (s) { var t = d.getElementById('js-position' + this.index); if (t && t.insertAdjacentElement) { t.insertAdjacentElement('afterend', s); } else { d.head.appendChild(s); } ++this.index; }, createScript: function (script, beforeLoad) { var s = d.createElement('script'); s.id = 'js-position' + (this.index + 1); s.setAttribute('data-test', script.test); if (beforeLoad) { s.defer = 'defer'; s.onload = function () { if (script.noinit) { loader.register(true); } if (d.readyState === 'interactive' || d.readyState === 'complete') { loader.ready(); } }; } else { s.async = 'async'; } s.src = script.src; return s; }, init: function () { this.scripts.forEach(function (s) { loader.insert(loader.createScript(s, true)); }); d.addEventListener('DOMContentLoaded', function () { loader.ready(); var conditionalScripts; conditionalScripts = [ {match: 'div[data-pan-container]', src: '/static/js/pan-zoom-es6-bundle-464a2af269.js', test: 'pan-zoom-js', module: true }, {match: 'div[data-pan-container]', src: '/static/js/pan-zoom-es5-bundle-98fb9b653b.js', test: 'pan-zoom-js', nomodule: true }, {match: 'math,span.mathjax-tex', src: '/static/js/math-es6-bundle-23597ae350.js', test: 'math-js', module: true}, {match: 'math,span.mathjax-tex', src: '/static/js/math-es5-bundle-6532c6f78b.js', test: 'math-js', nomodule: true} ]; if (conditionalScripts) { conditionalScripts.filter(function (script) { return !!document.querySelector(script.match) && !((moduleSupport && script.nomodule) || (!moduleSupport && script.module)); }).forEach(function (script) { loader.insert(loader.createScript(script)); }); } }, false); } }; loader.init(); } })(window, document); </script> <meta name="robots" content="noarchive"> <meta name="access" content="No"> <link rel="search" href="https://www.nature.com/search"> <link rel="search" href="https://www.nature.com/opensearch/opensearch.xml" type="application/opensearchdescription+xml" title="nature.com"> <link rel="search" href="https://www.nature.com/opensearch/request" type="application/sru+xml" title="nature.com"> <script type="application/ld+json">{"mainEntity":{"headline":"Sustained in situ protein production and release in the mammalian gut by an engineered bacteriophage","description":"Oral administration of biologic drugs is challenging because of the degradative activity of the upper gastrointestinal tract. Strategies that use engineered microbes to produce biologics in the lower gastrointestinal tract are limited by competition with resident commensal bacteria. Here we demonstrate the engineering of bacteriophage (phage) that infect resident commensals to express heterologous proteins released during cell lysis. Working with the virulent T4 phage, which targets resident, nonpathogenic Escherichia coli, we first identify T4-specific promoters with maximal protein expression and minimal impact on T4 phage titers. We engineer T4 phage to express a serine protease inhibitor of a pro-inflammatory enzyme with increased activity in ulcerative colitis and observe reduced enzyme activity in a mouse model of colitis. We also apply the approach to reduce weight gain and inflammation in mouse models of diet-induced obesity. This work highlights an application of virulent phages in the mammalian gut as engineerable vectors to release therapeutics from resident gut bacteria. Biologics are delivered to the gut using phage that infects resident commensal bacteria.","datePublished":"2025-02-18T00:00:00Z","dateModified":"2025-02-18T00:00:00Z","pageStart":"1","pageEnd":"10","sameAs":"https://doi.org/10.1038/s41587-025-02570-7","keywords":["Applied microbiology","Bacteriophages","Biotechnology","Life Sciences","general","Biomedicine","Agriculture","Biomedical Engineering/Biotechnology","Bioinformatics"],"image":["https://media.springernature.com/lw1200/springer-static/image/art%3A10.1038%2Fs41587-025-02570-7/MediaObjects/41587_2025_2570_Fig1_HTML.png","https://media.springernature.com/lw1200/springer-static/image/art%3A10.1038%2Fs41587-025-02570-7/MediaObjects/41587_2025_2570_Fig2_HTML.png","https://media.springernature.com/lw1200/springer-static/image/art%3A10.1038%2Fs41587-025-02570-7/MediaObjects/41587_2025_2570_Fig3_HTML.png","https://media.springernature.com/lw1200/springer-static/image/art%3A10.1038%2Fs41587-025-02570-7/MediaObjects/41587_2025_2570_Fig4_HTML.png","https://media.springernature.com/lw1200/springer-static/image/art%3A10.1038%2Fs41587-025-02570-7/MediaObjects/41587_2025_2570_Fig5_HTML.png"],"isPartOf":{"name":"Nature Biotechnology","issn":["1546-1696","1087-0156"],"@type":["Periodical"]},"publisher":{"name":"Nature Publishing Group US","logo":{"url":"https://www.springernature.com/app-sn/public/images/logo-springernature.png","@type":"ImageObject"},"@type":"Organization"},"author":[{"name":"Zachary R. Baker","affiliation":[{"name":"Virginia Tech","address":{"name":"Department of Biological Sciences, Virginia Tech, Blacksburg, USA","@type":"PostalAddress"},"@type":"Organization"},{"name":"Virginia Tech","address":{"name":"Fralin Life Sciences Institute, Virginia Tech, Blacksburg, USA","@type":"PostalAddress"},"@type":"Organization"},{"name":"Virginia Tech","address":{"name":"Center for Emerging, Zoonotic, and Arthropod-Borne Pathogens, Virginia Tech, Blacksburg, USA","@type":"PostalAddress"},"@type":"Organization"}],"@type":"Person"},{"name":"Yao Zhang","url":"http://orcid.org/0000-0002-0943-090X","affiliation":[{"name":"Virginia Tech","address":{"name":"Department of Biological Sciences, Virginia Tech, Blacksburg, USA","@type":"PostalAddress"},"@type":"Organization"}],"@type":"Person"},{"name":"Haiyan Zhang","affiliation":[{"name":"Virginia Tech","address":{"name":"Metabolism Core, Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, USA","@type":"PostalAddress"},"@type":"Organization"}],"@type":"Person"},{"name":"Hollyn C. Franklin","affiliation":[{"name":"Virginia Tech","address":{"name":"Department of Biological Sciences, Virginia Tech, Blacksburg, USA","@type":"PostalAddress"},"@type":"Organization"},{"name":"Virginia Tech","address":{"name":"Fralin Life Sciences Institute, Virginia Tech, Blacksburg, USA","@type":"PostalAddress"},"@type":"Organization"},{"name":"Virginia Tech","address":{"name":"Center for Emerging, Zoonotic, and Arthropod-Borne Pathogens, Virginia Tech, Blacksburg, USA","@type":"PostalAddress"},"@type":"Organization"}],"@type":"Person"},{"name":"Priscila B. S. Serpa","url":"http://orcid.org/0000-0001-6073-2172","affiliation":[{"name":"VA–MD College of Veterinary Medicine, Virginia Tech","address":{"name":"Department of Biomedical Sciences and Pathobiology, VA–MD College of Veterinary Medicine, Virginia Tech, Blacksburg, USA","@type":"PostalAddress"},"@type":"Organization"}],"@type":"Person"},{"name":"Teresa Southard","affiliation":[{"name":"VA–MD College of Veterinary Medicine, Virginia Tech","address":{"name":"Department of Biomedical Sciences and Pathobiology, VA–MD College of Veterinary Medicine, Virginia Tech, Blacksburg, USA","@type":"PostalAddress"},"@type":"Organization"}],"@type":"Person"},{"name":"Liwu Li","url":"http://orcid.org/0000-0001-8870-5299","affiliation":[{"name":"Virginia Tech","address":{"name":"Department of Biological Sciences, Virginia Tech, Blacksburg, USA","@type":"PostalAddress"},"@type":"Organization"}],"email":"lwli@vt.edu","@type":"Person"},{"name":"Bryan B. Hsu","url":"http://orcid.org/0000-0002-8219-1124","affiliation":[{"name":"Virginia Tech","address":{"name":"Department of Biological Sciences, Virginia Tech, Blacksburg, USA","@type":"PostalAddress"},"@type":"Organization"},{"name":"Virginia Tech","address":{"name":"Fralin Life Sciences Institute, Virginia Tech, Blacksburg, USA","@type":"PostalAddress"},"@type":"Organization"},{"name":"Virginia Tech","address":{"name":"Center for Emerging, Zoonotic, and Arthropod-Borne Pathogens, Virginia Tech, Blacksburg, USA","@type":"PostalAddress"},"@type":"Organization"},{"name":"VA–MD College of Veterinary Medicine, Virginia Tech","address":{"name":"Department of Biomedical Sciences and Pathobiology, VA–MD College of Veterinary Medicine, Virginia Tech, Blacksburg, USA","@type":"PostalAddress"},"@type":"Organization"}],"email":"bhsu@vt.edu","@type":"Person"}],"isAccessibleForFree":false,"hasPart":{"isAccessibleForFree":false,"cssSelector":".main-content","@type":"WebPageElement"},"@type":"ScholarlyArticle"},"@context":"https://schema.org","@type":"WebPage"}</script> <link rel="canonical" href="https://www.nature.com/articles/s41587-025-02570-7"> <meta name="journal_id" content="41587"/> <meta name="dc.title" content="Sustained in situ protein production and release in the mammalian gut by an engineered bacteriophage"/> <meta name="dc.source" content="Nature Biotechnology 2025"/> <meta name="dc.format" content="text/html"/> <meta name="dc.publisher" content="Nature Publishing Group"/> <meta name="dc.date" content="2025-02-18"/> <meta name="dc.type" content="OriginalPaper"/> <meta name="dc.language" content="En"/> <meta name="dc.copyright" content="2025 The Author(s), under exclusive licence to Springer Nature America, Inc."/> <meta name="dc.rights" content="2025 The Author(s), under exclusive licence to Springer Nature America, Inc."/> <meta name="dc.rightsAgent" content="journalpermissions@springernature.com"/> <meta name="dc.description" content="Oral administration of biologic drugs is challenging because of the degradative activity of the upper gastrointestinal tract. Strategies that use engineered microbes to produce biologics in the lower gastrointestinal tract are limited by competition with resident commensal bacteria. Here we demonstrate the engineering of bacteriophage (phage) that infect resident commensals to express heterologous proteins released during cell lysis. Working with the virulent T4 phage, which targets resident, nonpathogenic Escherichia coli, we first identify T4-specific promoters with maximal protein expression and minimal impact on T4 phage titers. We engineer T4 phage to express a serine protease inhibitor of a pro-inflammatory enzyme with increased activity in ulcerative colitis and observe reduced enzyme activity in a mouse model of colitis. We also apply the approach to reduce weight gain and inflammation in mouse models of diet-induced obesity. This work highlights an application of virulent phages in the mammalian gut as engineerable vectors to release therapeutics from resident gut bacteria. Biologics are delivered to the gut using phage that infects resident commensal bacteria."/> <meta name="prism.issn" content="1546-1696"/> <meta name="prism.publicationName" content="Nature Biotechnology"/> <meta name="prism.publicationDate" content="2025-02-18"/> <meta name="prism.section" content="OriginalPaper"/> <meta name="prism.startingPage" content="1"/> <meta name="prism.endingPage" content="10"/> <meta name="prism.copyright" content="2025 The Author(s), under exclusive licence to Springer Nature America, Inc."/> <meta name="prism.rightsAgent" content="journalpermissions@springernature.com"/> <meta name="prism.url" content="https://www.nature.com/articles/s41587-025-02570-7"/> <meta name="prism.doi" content="doi:10.1038/s41587-025-02570-7"/> <meta name="citation_pdf_url" content="https://www.nature.com/articles/s41587-025-02570-7.pdf"/> <meta name="citation_fulltext_html_url" content="https://www.nature.com/articles/s41587-025-02570-7"/> <meta name="citation_journal_title" content="Nature Biotechnology"/> <meta name="citation_journal_abbrev" content="Nat Biotechnol"/> <meta name="citation_publisher" content="Nature Publishing Group"/> <meta name="citation_issn" content="1546-1696"/> <meta name="citation_title" content="Sustained in situ protein production and release in the mammalian gut by an engineered bacteriophage"/> <meta name="citation_online_date" content="2025/02/18"/> <meta name="citation_firstpage" content="1"/> <meta name="citation_lastpage" content="10"/> <meta name="citation_article_type" content="Article"/> <meta name="citation_language" content="en"/> <meta name="dc.identifier" content="doi:10.1038/s41587-025-02570-7"/> <meta name="DOI" content="10.1038/s41587-025-02570-7"/> <meta name="size" content="239412"/> <meta name="citation_doi" content="10.1038/s41587-025-02570-7"/> <meta name="citation_springer_api_url" content="http://api.springer.com/xmldata/jats?q=doi:10.1038/s41587-025-02570-7&api_key="/> <meta name="description" content="Oral administration of biologic drugs is challenging because of the degradative activity of the upper gastrointestinal tract. Strategies that use engineered microbes to produce biologics in the lower gastrointestinal tract are limited by competition with resident commensal bacteria. Here we demonstrate the engineering of bacteriophage (phage) that infect resident commensals to express heterologous proteins released during cell lysis. Working with the virulent T4 phage, which targets resident, nonpathogenic Escherichia coli, we first identify T4-specific promoters with maximal protein expression and minimal impact on T4 phage titers. We engineer T4 phage to express a serine protease inhibitor of a pro-inflammatory enzyme with increased activity in ulcerative colitis and observe reduced enzyme activity in a mouse model of colitis. We also apply the approach to reduce weight gain and inflammation in mouse models of diet-induced obesity. This work highlights an application of virulent phages in the mammalian gut as engineerable vectors to release therapeutics from resident gut bacteria. Biologics are delivered to the gut using phage that infects resident commensal bacteria."/> <meta name="dc.creator" content="Baker, Zachary R."/> <meta name="dc.creator" content="Zhang, Yao"/> <meta name="dc.creator" content="Zhang, Haiyan"/> <meta name="dc.creator" content="Franklin, Hollyn C."/> <meta name="dc.creator" content="Serpa, Priscila B. S."/> <meta name="dc.creator" content="Southard, Teresa"/> <meta name="dc.creator" content="Li, Liwu"/> <meta name="dc.creator" content="Hsu, Bryan B."/> <meta name="dc.subject" content="Applied microbiology"/> <meta name="dc.subject" content="Bacteriophages"/> <meta name="dc.subject" content="Biotechnology"/> <meta name="citation_reference" content="citation_journal_title=Front. Pharmacol.; citation_title=Advances in oral drug delivery for regional targeting in the gastrointestinal tract—influence of physiological, pathophysiological and pharmaceutical factors; citation_author=S Hua; citation_volume=11; citation_publication_date=2020; citation_pages=524; citation_doi=10.3389/fphar.2020.00524; citation_id=CR1"/> <meta name="citation_reference" content="citation_journal_title=Pharmaceutics; citation_title=Currentstate and future perspectives on gastroretentive drug delivery systems; citation_author=J Tripathi, P Thapa, R Maharjan, SH Jeong; citation_volume=11; citation_publication_date=2019; citation_pages=193; citation_doi=10.3390/pharmaceutics11040193; citation_id=CR2"/> <meta name="citation_reference" content="citation_journal_title=Pharmaceutics; citation_title=Oral delivery of biologics via the intestine; citation_author=R New; citation_volume=13; citation_publication_date=2020; citation_pages=18; citation_doi=10.3390/pharmaceutics13010018; citation_id=CR3"/> <meta name="citation_reference" content="citation_journal_title=Pharmaceutics; citation_title=Intestinal permeability and drug absorption: predictive experimental, computational and in vivo approaches; citation_author=D Dahlgren, H Lennernas; citation_volume=11; citation_publication_date=2019; citation_pages=411; citation_doi=10.3390/pharmaceutics11080411; citation_id=CR4"/> <meta name="citation_reference" content="citation_journal_title=Mayo Clin. Proc.; citation_title=Medication adherence: WHO cares?; citation_author=MT Brown, JK Bussell; citation_volume=86; citation_publication_date=2011; citation_pages=304-314; citation_doi=10.4065/mcp.2010.0575; citation_id=CR5"/> <meta name="citation_reference" content="citation_journal_title=Nat. Rev. Drug Discov.; citation_title=The prospect for bacteriophage therapy in Western medicine; citation_author=CR Merril, D Scholl, SL Adhya; citation_volume=2; citation_publication_date=2003; citation_pages=489-497; citation_doi=10.1038/nrd1111; citation_id=CR6"/> <meta name="citation_reference" content="citation_journal_title=Proc. Natl Acad. Sci. USA; citation_title=Bacteriophage adhering to mucus provide a non-host-derived immunity; citation_author=JJ Barr; citation_volume=110; citation_publication_date=2013; citation_pages=10771-10776; citation_doi=10.1073/pnas.1305923110; citation_id=CR7"/> <meta name="citation_reference" content="citation_journal_title=Viruses; citation_title=Interactions between bacteriophage, bacteria, and the mammalian immune system; citation_author=JD Van Belleghem, K Dabrowska, M Vaneechoutte, JJ Barr, PL Bollyky; citation_volume=11; citation_publication_date=2018; citation_pages=10; citation_doi=10.3390/v11010010; citation_id=CR8"/> <meta name="citation_reference" content="citation_journal_title=Cell Host Microbe; citation_title=The human gut virome is highly diverse, stable, and individual specific; citation_author=AN Shkoporov; citation_volume=26; citation_publication_date=2019; citation_pages=527-541 e525; citation_doi=10.1016/j.chom.2019.09.009; citation_id=CR9"/> <meta name="citation_reference" content="citation_journal_title=Proc. Natl Acad. Sci. USA; citation_title=Rapid evolution of the human gut virome; citation_author=S Minot; citation_volume=110; citation_publication_date=2013; citation_pages=12450-12455; citation_doi=10.1073/pnas.1300833110; citation_id=CR10"/> <meta name="citation_reference" content="citation_journal_title=Nat. Commun.; citation_title=PhiCrAss001 represents the most abundant bacteriophage family in the human gut and infects Bacteroides intestinalis; citation_author=AN Shkoporov; citation_volume=9; citation_publication_date=2018; citation_doi=10.1038/s41467-018-07225-7; citation_id=CR11"/> <meta name="citation_reference" content="citation_journal_title=Virology; citation_title=In vivo replication of T4 and T7 bacteriophages in germ-free mice colonized with Escherichia coli; citation_author=M Weiss; citation_volume=393; citation_publication_date=2009; citation_pages=16-23; citation_doi=10.1016/j.virol.2009.07.020; citation_id=CR12"/> <meta name="citation_reference" content="citation_journal_title=Cell Host Microbe; citation_title=Dynamic modulation of the gut microbiota and metabolome by bacteriophages in a mouse model; citation_author=BB Hsu; citation_volume=25; citation_publication_date=2019; citation_pages=803-814; citation_doi=10.1016/j.chom.2019.05.001; citation_id=CR13"/> <meta name="citation_reference" content="citation_journal_title=Environ. Microbiol.; citation_title=Intestinal colonization by enteroaggregative Escherichia coli supports long-term bacteriophage replication in mice; citation_author=D Maura; citation_volume=14; citation_publication_date=2012; citation_pages=1844-1854; citation_doi=10.1111/j.1462-2920.2011.02644.x; citation_id=CR14"/> <meta name="citation_reference" content="citation_journal_title=Clin. Microbiol. Rev.; citation_title=Intestinal bacteriophage therapy: looking for optimal efficacy; citation_author=F Javaudin, C Latour, L Debarbieux, Q Lamy-Besnier; citation_volume=34; citation_publication_date=2021; citation_pages=e0013621; citation_doi=10.1128/CMR.00136-21; citation_id=CR15"/> <meta name="citation_reference" content="citation_journal_title=Transl. Psychiatry; citation_title=Bacterial ClpB heat-shock protein, an antigen-mimetic of the anorexigenic peptide α-MSH, at the origin of eating disorders; citation_author=N Tennoune; citation_volume=4; citation_publication_date=2014; citation_doi=10.1038/tp.2014.98; citation_id=CR16"/> <meta name="citation_reference" content="citation_journal_title=Int. J. Obes.; citation_title=Commensal Hafnia alvei strain reduces food intake and fat mass in obese mice—a new potential probiotic for appetite and body weight management; citation_author=R Legrand; citation_volume=44; citation_publication_date=2020; citation_pages=1041-1051; citation_doi=10.1038/s41366-019-0515-9; citation_id=CR17"/> <meta name="citation_reference" content="citation_journal_title=Microbiol. Mol. Biol. Rev.; citation_title=Bacteriophage T4 genome; citation_author=ES Miller; citation_volume=67; citation_publication_date=2003; citation_pages=86-156; citation_doi=10.1128/MMBR.67.1.86-156.2003; citation_id=CR18"/> <meta name="citation_reference" content="citation_journal_title=Virology; citation_title=Microarray analysis of gene expression during bacteriophage T4 infection; citation_author=K Luke; citation_volume=299; citation_publication_date=2002; citation_pages=182-191; citation_doi=10.1006/viro.2002.1409; citation_id=CR19"/> <meta name="citation_reference" content="Grigonyte, A. Engineering Bacteriophages to Enhance their Potential Use in Therapy (University of Warwick, 2018)."/> <meta name="citation_reference" content="citation_journal_title=Analyst; citation_title=Phage-based biosensors: in vivo analysis of native T4 phage promoters to enhance reporter enzyme expression; citation_author=MM Duong, CM Carmody, SR Nugen; citation_volume=145; citation_publication_date=2020; citation_pages=6291-6297; citation_doi=10.1039/D0AN01413C; citation_id=CR21"/> <meta name="citation_reference" content="citation_journal_title=J. Bacteriol.; citation_title=ModA and ModB, two ADP-ribosyltransferases encoded by bacteriophage T4: catalytic properties and mutation analysis; citation_author=B Tiemann; citation_volume=186; citation_publication_date=2004; citation_pages=7262-7272; citation_doi=10.1128/JB.186.21.7262-7272.2004; citation_id=CR22"/> <meta name="citation_reference" content="citation_journal_title=Proc. Natl Acad. Sci. USA; citation_title=Molecular architecture of the prolate head of bacteriophage T4; citation_author=A Fokine; citation_volume=101; citation_publication_date=2004; citation_pages=6003-6008; citation_doi=10.1073/pnas.0400444101; citation_id=CR23"/> <meta name="citation_reference" content="citation_journal_title=Future Microbiol.; citation_title=Structure and function of bacteriophage T4; citation_author=ML Yap, MG Rossmann; citation_volume=9; citation_publication_date=2014; citation_pages=1319-1327; citation_doi=10.2217/fmb.14.91; citation_id=CR24"/> <meta name="citation_reference" content="citation_journal_title=Infect. Immun.; citation_title=Mouse intestine selects nonmotile flhDC mutants of Escherichia coli MG1655 with increased colonizing ability and better utilization of carbon sources; citation_author=MP Leatham; citation_volume=73; citation_publication_date=2005; citation_pages=8039-8049; citation_doi=10.1128/IAI.73.12.8039-8049.2005; citation_id=CR25"/> <meta name="citation_reference" content="citation_journal_title=Infect. Immun.; citation_title=The Escherichia coli K-12 gntP gene allows E. coli F-18 to occupy a distinct nutritional niche in the streptomycin-treated mouse large intestine; citation_author=NJ Sweeney; citation_volume=64; citation_publication_date=1996; citation_pages=3497-3503; citation_doi=10.1128/iai.64.9.3497-3503.1996; citation_id=CR26"/> <meta name="citation_reference" content="citation_journal_title=J. Inflamm. Res.; citation_title=Human neutrophil elastase proteolytic activity in ulcerative colitis favors the loss of function of therapeutic monoclonal antibodies; citation_author=R Curciarello; citation_volume=13; citation_publication_date=2020; citation_pages=233-243; citation_doi=10.2147/JIR.S234710; citation_id=CR27"/> <meta name="citation_reference" content="citation_journal_title=Mucosal Immunol.; citation_title=Faecal neutrophil elastase-antiprotease balance reflects colitis severity; citation_author=R Barry; citation_volume=13; citation_publication_date=2020; citation_pages=322-333; citation_doi=10.1038/s41385-019-0235-4; citation_id=CR28"/> <meta name="citation_reference" content="citation_journal_title=Cell Mol. Immunol.; citation_title=Neutrophils in chronic inflammatory diseases; citation_author=A Herrero-Cervera, O Soehnlein, E Kenne; citation_volume=19; citation_publication_date=2022; citation_pages=177-191; citation_doi=10.1038/s41423-021-00832-3; citation_id=CR29"/> <meta name="citation_reference" content="citation_journal_title=J. Gastroenterol.; citation_title=Inhibition of neutrophil elastase prevents the development of murine dextran sulfate sodium-induced colitis; citation_author=Y Morohoshi; citation_volume=41; citation_publication_date=2006; citation_pages=318-324; citation_doi=10.1007/s00535-005-1768-8; citation_id=CR30"/> <meta name="citation_reference" content="citation_journal_title=Front. Immunol.; citation_title=Serpinb1a is dispensable for the development and cytokine response of invariant natural killer T cell subsets; citation_author=NGF Leborgne, A Taddeo, S Freigang, C Benarafa; citation_volume=11; citation_publication_date=2020; citation_pages=562587; citation_doi=10.3389/fimmu.2020.562587; citation_id=CR31"/> <meta name="citation_reference" content="citation_journal_title=Inflamm. Res.; citation_title=Resolving neutrophils due to TRAM deletion renders protection against experimental sepsis; citation_author=R Lin; citation_volume=72; citation_publication_date=2023; citation_pages=1733-1744; citation_doi=10.1007/s00011-023-01779-z; citation_id=CR32"/> <meta name="citation_reference" content="citation_journal_title=EMBO Mol. Med.; citation_title=Immune-enhancing neutrophils reprogrammed by subclinical low-dose endotoxin in cancer treatment; citation_author=Y Zhang; citation_volume=16; citation_publication_date=2024; citation_pages=1886-1900; citation_doi=10.1038/s44321-024-00100-7; citation_id=CR33"/> <meta name="citation_reference" content="citation_journal_title=Science; citation_title=CD24 and Siglec-10 selectively repress tissue damage-induced immune responses; citation_author=GY Chen, J Tang, P Zheng, Y Liu; citation_volume=323; citation_publication_date=2009; citation_pages=1722-1725; citation_doi=10.1126/science.1168988; citation_id=CR34"/> <meta name="citation_reference" content="citation_journal_title=Mucosal Immunol.; citation_title=Gut mucosal DAMPs in IBD: from mechanisms to therapeutic implications; citation_author=RK Boyapati, AG Rossi, J Satsangi, GT Ho; citation_volume=9; citation_publication_date=2016; citation_pages=567-582; citation_doi=10.1038/mi.2016.14; citation_id=CR35"/> <meta name="citation_reference" content="citation_journal_title=Circ. Res.; citation_title=Monocytes reprogrammed by 4-PBA potently contribute to the resolution of inflammation and atherosclerosis; citation_author=S Geng; citation_volume=135; citation_publication_date=2024; citation_pages=856-872; citation_doi=10.1161/CIRCRESAHA.124.325023; citation_id=CR36"/> <meta name="citation_reference" content="citation_journal_title=Cell Metab.; citation_title=CD24-Siglec axis is an innate immune checkpoint against metaflammation and metabolic disorder; citation_author=X Wang; citation_volume=34; citation_publication_date=2022; citation_pages=1088-1103; citation_doi=10.1016/j.cmet.2022.07.005; citation_id=CR37"/> <meta name="citation_reference" content="citation_journal_title=Inflamm. Bowel Dis.; citation_title=CD24 is upregulated in inflammatory bowel disease and stimulates cell motility and colony formation; citation_author=MA Ahmed; citation_volume=16; citation_publication_date=2010; citation_pages=795-803; citation_doi=10.1002/ibd.21134; citation_id=CR38"/> <meta name="citation_reference" content="citation_journal_title=Nutrients; citation_title=The probiotic strain H. alvei HA4597((R)) improves weight loss in overweight subjects under moderate hypocaloric diet: a proof-of-concept, multicenter randomized, double-blind placebo-controlled study; citation_author=P Dechelotte; citation_volume=13; citation_publication_date=2021; citation_pages=1902; citation_doi=10.3390/nu13061902; citation_id=CR39"/> <meta name="citation_reference" content="citation_journal_title=Nutrients; citation_title=Effects of bacterial CLPB protein fragments on food intake and PYY secretion; citation_author=M Dominique; citation_volume=13; citation_publication_date=2021; citation_pages=2223; citation_doi=10.3390/nu13072223; citation_id=CR40"/> <meta name="citation_reference" content="citation_journal_title=Cell Metab.; citation_title=The melanocortin-4 receptor is expressed in enteroendocrine L cells and regulates the release of peptide YY and glucagon-like peptide 1 in vivo; citation_author=BL Panaro; citation_volume=20; citation_publication_date=2014; citation_pages=1018-1029; citation_doi=10.1016/j.cmet.2014.10.004; citation_id=CR41"/> <meta name="citation_reference" content="citation_journal_title=Mol. Metab.; citation_title=The melanocortin pathway and energy homeostasis: from discovery to obesity therapy; citation_author=GSH Yeo; citation_volume=48; citation_publication_date=2021; citation_pages=101206; citation_doi=10.1016/j.molmet.2021.101206; citation_id=CR42"/> <meta name="citation_reference" content="citation_journal_title=Cell Host Microbe; citation_title=The spatial heterogeneity of the gut limits predation and fosters coexistence of bacteria and bacteriophages; citation_author=M Lourenco; citation_volume=28; citation_publication_date=2020; citation_pages=390-401; citation_doi=10.1016/j.chom.2020.06.002; citation_id=CR43"/> <meta name="citation_reference" content="citation_journal_title=Infect. Immun.; citation_title=Fitness trade-offs resulting from bacteriophage resistance potentiate synergistic antibacterial strategies; citation_author=MR Mangalea, BA Duerkop; citation_volume=88; citation_publication_date=2020; citation_pages=e00926; citation_doi=10.1128/IAI.00926-19; citation_id=CR44"/> <meta name="citation_reference" content="citation_journal_title=J. Clin. Invest.; citation_title=Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance; citation_author=H Xu; citation_volume=112; citation_publication_date=2003; citation_pages=1821-1830; citation_doi=10.1172/JCI200319451; citation_id=CR45"/> <meta name="citation_reference" content="citation_journal_title=Nature; citation_title=Inflammation and metabolic disorders; citation_author=GS Hotamisligil; citation_volume=444; citation_publication_date=2006; citation_pages=860-867; citation_doi=10.1038/nature05485; citation_id=CR46"/> <meta name="citation_reference" content="citation_journal_title=J. Clin. Invest.; citation_title=Inflammation, stress, and diabetes; citation_author=KE Wellen, GS Hotamisligil; citation_volume=115; citation_publication_date=2005; citation_pages=1111-1119; citation_doi=10.1172/JCI25102; citation_id=CR47"/> <meta name="citation_reference" content="citation_journal_title=Immunology; citation_title=Interleukin-23: as a drug target for autoimmune inflammatory diseases; citation_author=C Tang, S Chen, H Qian, W Huang; citation_volume=135; citation_publication_date=2012; citation_pages=112-124; citation_doi=10.1111/j.1365-2567.2011.03522.x; citation_id=CR48"/> <meta name="citation_reference" content="citation_journal_title=Immunology; citation_title=Interleukin-23 promotes intestinal T helper type17 immunity and ameliorates obesity-associated metabolic syndrome in a murine high-fat diet model; citation_author=LMS Martins; citation_volume=154; citation_publication_date=2018; citation_pages=624-636; citation_doi=10.1111/imm.12946; citation_id=CR49"/> <meta name="citation_reference" content="citation_journal_title=Int. J. Obes.; citation_title=Increased activity of interleukin-23/interleukin-17 proinflammatory axis in obese women; citation_author=M Sumarac-Dumanovic; citation_volume=33; citation_publication_date=2009; citation_pages=151-156; citation_doi=10.1038/ijo.2008.216; citation_id=CR50"/> <meta name="citation_reference" content="citation_journal_title=J. Clin. Invest.; citation_title=The IL-23/IL-17 axis in inflammation; citation_author=Y Iwakura, H Ishigame; citation_volume=116; citation_publication_date=2006; citation_pages=1218-1222; citation_doi=10.1172/JCI28508; citation_id=CR51"/> <meta name="citation_reference" content="citation_journal_title=J. Clin. Invest.; citation_title=MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity; citation_author=H Kanda; citation_volume=116; citation_publication_date=2006; citation_pages=1494-1505; citation_doi=10.1172/JCI26498; citation_id=CR52"/> <meta name="citation_reference" content="citation_journal_title=Cytokine; citation_title=Monocyte chemoattractant protein 1 (MCP-1) in obesity and diabetes; citation_author=J Panee; citation_volume=60; citation_publication_date=2012; citation_pages=1-12; citation_doi=10.1016/j.cyto.2012.06.018; citation_id=CR53"/> <meta name="citation_reference" content="citation_journal_title=Proc. Natl Acad. Sci. USA; citation_title=Monocyte chemoattractant protein 1 in obesity and insulin resistance; citation_author=P Sartipy, DJ Loskutoff; citation_volume=100; citation_publication_date=2003; citation_pages=7265-7270; citation_doi=10.1073/pnas.1133870100; citation_id=CR54"/> <meta name="citation_reference" content="citation_journal_title=Gut Microbes; citation_title=Involvement of gut microbiota in the development of low-grade inflammation and type 2 diabetes associated with obesity; citation_author=PD Cani, M Osto, L Geurts, A Everard; citation_volume=3; citation_publication_date=2012; citation_pages=279-288; citation_doi=10.4161/gmic.19625; citation_id=CR55"/> <meta name="citation_reference" content="citation_journal_title=J. Mol. Biol.; citation_title=Bacteriophage T4 host range is expanded by duplications of a small domain of the tail fiber adhesin; citation_author=F Tetart, F Repoila, C Monod, HM Krisch; citation_volume=258; citation_publication_date=1996; citation_pages=726-731; citation_doi=10.1006/jmbi.1996.0281; citation_id=CR56"/> <meta name="citation_reference" content="citation_journal_title=Proc. Natl Acad. Sci. USA; citation_title=Human gut microbiota in obesity and after gastric bypass; citation_author=H Zhang; citation_volume=106; citation_publication_date=2009; citation_pages=2365-2370; citation_doi=10.1073/pnas.0812600106; citation_id=CR57"/> <meta name="citation_reference" content="citation_journal_title=BMC Microbiol.; citation_title=Comparative analysis of gut microbiota associated with body mass index in a large Korean cohort; citation_author=Y Yun; citation_volume=17; citation_publication_date=2017; citation_pages=151; citation_doi=10.1186/s12866-017-1052-0; citation_id=CR58"/> <meta name="citation_reference" content="citation_journal_title=Nat. Microbiol.; citation_title=Global phylogeography and ancient evolution of the widespread human gut virus crAssphage; citation_author=RA Edwards; citation_volume=4; citation_publication_date=2019; citation_pages=1727-1736; citation_doi=10.1038/s41564-019-0494-6; citation_id=CR59"/> <meta name="citation_reference" content="citation_journal_title=Nat. Commun.; citation_title=Developing a new class of engineered live bacterial therapeutics to treat human diseases; citation_author=MR Charbonneau, VM Isabella, N Li, CB Kurtz; citation_volume=11; citation_publication_date=2020; citation_doi=10.1038/s41467-020-15508-1; citation_id=CR60"/> <meta name="citation_reference" content="citation_journal_title=Nat. Biotechnol.; citation_title=Development of a synthetic live bacterial therapeutic for the human metabolic disease phenylketonuria; citation_author=VM Isabella; citation_volume=36; citation_publication_date=2018; citation_pages=857-864; citation_doi=10.1038/nbt.4222; citation_id=CR61"/> <meta name="citation_reference" content="citation_journal_title=Sci. Transl. Med.; citation_title=An engineered E. coli Nissle improves hyperammonemia and survival in mice and shows dose-dependent exposure in healthy humans; citation_author=CB Kurtz; citation_volume=11; citation_publication_date=2019; citation_pages=eaau7975; citation_doi=10.1126/scitranslmed.aau7975; citation_id=CR62"/> <meta name="citation_reference" content="citation_journal_title=Antimicrob. Agents Chemother.; citation_title=Virulent bacteriophages can target O104:H4 enteroaggregative Escherichia coli in the mouse intestine; citation_author=D Maura, M Galtier, C Bouguenec, L Debarbieux; citation_volume=56; citation_publication_date=2012; citation_pages=6235-6242; citation_doi=10.1128/AAC.00602-12; citation_id=CR63"/> <meta name="citation_reference" content="citation_journal_title=Virol J.; citation_title=Transcription of the T4 late genes; citation_author=EP Geiduschek, GA Kassavetis; citation_volume=7; citation_publication_date=2010; citation_pages=288; citation_doi=10.1186/1743-422X-7-288; citation_id=CR64"/> <meta name="citation_reference" content="Stirling, F. et al. Rational design of evolutionarily stable microbial kill switches. Mol. Cell 68, 686–697 (2017)."/> <meta name="citation_reference" content="citation_journal_title=Nat. Commun.; citation_title=Genetically stable CRISPR-based kill switches for engineered microbes; citation_author=AG Rottinghaus, A Ferreiro, SRS Fishbein, G Dantas, TS Moon; citation_volume=13; citation_publication_date=2022; citation_doi=10.1038/s41467-022-28163-5; citation_id=CR66"/> <meta name="citation_reference" content="citation_journal_title=Microbiologyopen; citation_title=Quantitative analysis of commensal Escherichia coli populations reveals host-specific enterotypes at the intra-species level; citation_author=M Smati; citation_volume=4; citation_publication_date=2015; citation_pages=604-615; citation_doi=10.1002/mbo3.266; citation_id=CR67"/> <meta name="citation_reference" content="citation_journal_title=Nat. Rev. Microbiol.; citation_title=The population genetics of commensal Escherichia coli; citation_author=O Tenaillon, D Skurnik, B Picard, E Denamur; citation_volume=8; citation_publication_date=2010; citation_pages=207-217; citation_doi=10.1038/nrmicro2298; citation_id=CR68"/> <meta name="citation_reference" content="citation_journal_title=Cell; citation_title=Phage therapy: from biological mechanisms to future directions; citation_author=SA Strathdee, GF Hatfull, VK Mutalik, RT Schooley; citation_volume=186; citation_publication_date=2023; citation_pages=17-31; citation_doi=10.1016/j.cell.2022.11.017; citation_id=CR69"/> <meta name="citation_reference" content="citation_journal_title=Cell Host Microbe; citation_title=Expansion of bacteriophages is linked to aggravated intestinal inflammation and colitis; citation_author=L Gogokhia; citation_volume=25; citation_publication_date=2019; citation_pages=285-299; citation_doi=10.1016/j.chom.2019.01.008; citation_id=CR70"/> <meta name="citation_reference" content="citation_journal_title=mBio; citation_title=Bacteriophage transcytosis provides a mechanism to cross epithelial cell layers; citation_author=S Nguyen; citation_volume=8; citation_publication_date=2017; citation_pages=e01874; citation_doi=10.1128/mBio.01874-17; citation_id=CR71"/> <meta name="citation_reference" content="citation_journal_title=Cell Host Microbe; citation_title=Whole-virome analysis sheds light on viral dark matter in inflammatory bowel disease; citation_author=AG Clooney; citation_volume=26; citation_publication_date=2019; citation_pages=764-778; citation_doi=10.1016/j.chom.2019.10.009; citation_id=CR72"/> <meta name="citation_reference" content="citation_journal_title=PLoS ONE; citation_title=A one pot, one step, precision cloning method with high throughput capability; citation_author=C Engler, R Kandzia, S Marillonnet; citation_volume=3; citation_publication_date=2008; citation_pages=e3647; citation_doi=10.1371/journal.pone.0003647; citation_id=CR73"/> <meta name="citation_reference" content="citation_journal_title=J. Biol. Eng.; citation_title=Study of in vitro transcriptional binding effects and noise using constitutive promoters combined with UP element sequences in Escherichia coli; citation_author=Q Yan, SS Fong; citation_volume=11; citation_publication_date=2017; citation_doi=10.1186/s13036-017-0075-2; citation_id=CR74"/> <meta name="citation_reference" content="citation_journal_title=Cell; citation_title=Repurposing CRISPR as an RNA-guided platform for sequence-specific control of gene expression; citation_author=LS Qi; citation_volume=152; citation_publication_date=2013; citation_pages=1173-1183; citation_doi=10.1016/j.cell.2013.02.022; citation_id=CR75"/> <meta name="citation_reference" content="citation_journal_title=Proc. Natl Acad. Sci. USA; citation_title=Acriflavine resistance: a bacteriophage mutation affecting the uptake of dye by the infected bacterial cells; citation_author=S Silver; citation_volume=53; citation_publication_date=1965; citation_pages=24-30; citation_doi=10.1073/pnas.53.1.24; citation_id=CR76"/> <meta name="citation_reference" content="citation_journal_title=Genetics; citation_title=The spectrum of acridine resistant mutants of bacteriophage T4 reveals cryptic effects of the tsL141 DNA polymerase allele on spontaneous mutagenesis; citation_author=FJ Wang, LS Ripley; citation_volume=148; citation_publication_date=1998; citation_pages=1655-1665; citation_doi=10.1093/genetics/148.4.1655; citation_id=CR77"/> <meta name="citation_reference" content="citation_journal_title=Biochemistry; citation_title=An improved method for bacterial immunofluorescence staining to eliminate antibody exclusion from the fixed nucleoid; citation_author=S Park, MA Reyer, EL McLean, W Liu, J Fei; citation_volume=58; citation_publication_date=2019; citation_pages=4457-4465; citation_doi=10.1021/acs.biochem.9b00724; citation_id=CR78"/> <meta name="citation_reference" content="citation_journal_title=PLoS Biol.; citation_title=Viruses’ life history: towards a mechanistic basis of a trade-off between survival and reproduction among phages; citation_author=M Paepe, F Taddei; citation_volume=4; citation_publication_date=2006; citation_pages=e193; citation_doi=10.1371/journal.pbio.0040193; citation_id=CR79"/> <meta name="citation_reference" content="Weichhart, T. mTor: Methods and Protocols (Humana Press, 2012)."/> <meta name="citation_reference" content="Charles River Research Model. C57BL/6 Mouse Clinical Pathology Data, C57BL/6 mouse hematology: North American colonies. (2012)."/> <meta name="citation_reference" content="citation_journal_title=Nat. Biotechnol.; citation_title=Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2; citation_author=E Bolyen; citation_volume=37; citation_publication_date=2019; citation_pages=852-857; citation_doi=10.1038/s41587-019-0209-9; citation_id=CR82"/> <meta name="citation_reference" content="citation_journal_title=Nat. Methods; citation_title=DADA2: high-resolution sample inference from Illumina amplicon data; citation_author=BJ Callahan; citation_volume=13; citation_publication_date=2016; citation_pages=581-583; citation_doi=10.1038/nmeth.3869; citation_id=CR83"/> <meta name="citation_reference" content="citation_journal_title=PLoS ONE; citation_title=Preservation of three-dimensional spatial structure in the gut microbiome; citation_author=Y Hasegawa, JL Mark Welch, BJ Rossetti, GG Borisy; citation_volume=12; citation_publication_date=2017; citation_pages=e0188257; citation_doi=10.1371/journal.pone.0188257; citation_id=CR84"/> <meta name="citation_reference" content="Baker, Z. 16S Illumina sequencing reads. Mendeley Data data.mendeley.com/datasets/pt9m6b9s4z/1 (2024)."/> <meta name="citation_author" content="Baker, Zachary R."/> <meta name="citation_author_institution" content="Department of Biological Sciences, Virginia Tech, Blacksburg, USA"/> <meta name="citation_author_institution" content="Fralin Life Sciences Institute, Virginia Tech, Blacksburg, USA"/> <meta name="citation_author_institution" content="Center for Emerging, Zoonotic, and Arthropod-Borne Pathogens, Virginia Tech, Blacksburg, USA"/> <meta name="citation_author" content="Zhang, Yao"/> <meta name="citation_author_institution" content="Department of Biological Sciences, Virginia Tech, Blacksburg, USA"/> <meta name="citation_author" content="Zhang, Haiyan"/> <meta name="citation_author_institution" content="Metabolism Core, Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, USA"/> <meta name="citation_author" content="Franklin, Hollyn C."/> <meta name="citation_author_institution" content="Department of Biological Sciences, Virginia Tech, Blacksburg, USA"/> <meta name="citation_author_institution" content="Fralin Life Sciences Institute, Virginia Tech, Blacksburg, USA"/> <meta name="citation_author_institution" content="Center for Emerging, Zoonotic, and Arthropod-Borne Pathogens, Virginia Tech, Blacksburg, USA"/> <meta name="citation_author" content="Serpa, Priscila B. S."/> <meta name="citation_author_institution" content="Department of Biomedical Sciences and Pathobiology, VA–MD College of Veterinary Medicine, Virginia Tech, Blacksburg, USA"/> <meta name="citation_author" content="Southard, Teresa"/> <meta name="citation_author_institution" content="Department of Biomedical Sciences and Pathobiology, VA–MD College of Veterinary Medicine, Virginia Tech, Blacksburg, USA"/> <meta name="citation_author" content="Li, Liwu"/> <meta name="citation_author_institution" content="Department of Biological Sciences, Virginia Tech, Blacksburg, USA"/> <meta name="citation_author" content="Hsu, Bryan B."/> <meta name="citation_author_institution" content="Department of Biological Sciences, Virginia Tech, Blacksburg, USA"/> <meta name="citation_author_institution" content="Fralin Life Sciences Institute, Virginia Tech, Blacksburg, USA"/> <meta name="citation_author_institution" content="Center for Emerging, Zoonotic, and Arthropod-Borne Pathogens, Virginia Tech, Blacksburg, USA"/> <meta name="citation_author_institution" content="Department of Biomedical Sciences and Pathobiology, VA–MD College of Veterinary Medicine, Virginia Tech, Blacksburg, USA"/> <meta name="access_endpoint" content="https://www.nature.com/platform/readcube-access"/> <meta name="twitter:site" content="@NatureBiotech"/> <meta name="twitter:card" content="summary_large_image"/> <meta name="twitter:image:alt" content="Content cover image"/> <meta name="twitter:title" content="Sustained in situ protein production and release in the mammalian gut by an engineered bacteriophage"/> <meta name="twitter:description" content="Nature Biotechnology - Biologics are delivered to the gut using phage that infects resident commensal bacteria."/> <meta name="twitter:image" content="https://media.springernature.com/full/springer-static/image/art%3A10.1038%2Fs41587-025-02570-7/MediaObjects/41587_2025_2570_Fig1_HTML.png"/> <meta property="og:url" content="https://www.nature.com/articles/s41587-025-02570-7"/> <meta property="og:type" content="article"/> <meta property="og:site_name" content="Nature"/> <meta property="og:title" content="Sustained in situ protein production and release in the mammalian gut by an engineered bacteriophage - Nature Biotechnology"/> <meta property="og:description" content="Biologics are delivered to the gut using phage that infects resident commensal bacteria."/> <meta property="og:image" content="https://media.springernature.com/m685/springer-static/image/art%3A10.1038%2Fs41587-025-02570-7/MediaObjects/41587_2025_2570_Fig1_HTML.png"/> <script> window.eligibleForRa21 = 'true'; </script> </head> <body class="article-page"> <noscript><iframe src="https://www.googletagmanager.com/ns.html?id=GTM-MRVXSHQ" height="0" width="0" style="display:none;visibility:hidden"></iframe></noscript> <div class="position-relative cleared z-index-50 background-white" data-test="top-containers"> <a class="c-skip-link" href="#content">Skip to main content</a> <div class="c-grade-c-banner u-hide"> <div class="c-grade-c-banner__container"> <p>Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.</p> </div> </div> <div class="u-hide u-show-following-ad"></div> <aside class="c-ad c-ad--728x90"> <div class="c-ad__inner" data-container-type="banner-advert"> <p class="c-ad__label">Advertisement</p> <div id="div-gpt-ad-top-1" class="div-gpt-ad advert leaderboard js-ad text-center hide-print grade-c-hide" data-ad-type="top" data-test="top-ad" data-pa11y-ignore data-gpt data-gpt-unitpath="/285/biotech.nature.com/article" data-gpt-sizes="728x90" data-gpt-targeting="type=article;pos=top;artid=s41587-025-02570-7;doi=10.1038/s41587-025-02570-7;subjmeta=1321,2522,326,61,631;kwrd=Applied+microbiology,Bacteriophages,Biotechnology"> <noscript> <a href="//pubads.g.doubleclick.net/gampad/jump?iu=/285/biotech.nature.com/article&sz=728x90&c=-2069840696&t=pos%3Dtop%26type%3Darticle%26artid%3Ds41587-025-02570-7%26doi%3D10.1038/s41587-025-02570-7%26subjmeta%3D1321,2522,326,61,631%26kwrd%3DApplied+microbiology,Bacteriophages,Biotechnology"> <img data-test="gpt-advert-fallback-img" src="//pubads.g.doubleclick.net/gampad/ad?iu=/285/biotech.nature.com/article&sz=728x90&c=-2069840696&t=pos%3Dtop%26type%3Darticle%26artid%3Ds41587-025-02570-7%26doi%3D10.1038/s41587-025-02570-7%26subjmeta%3D1321,2522,326,61,631%26kwrd%3DApplied+microbiology,Bacteriophages,Biotechnology" alt="Advertisement" width="728" height="90"></a> </noscript> </div> </div> </aside> <header class="c-header" id="header" data-header data-track-component="nature-150-split-header" style="border-color:#efd600"> <div class="c-header__row"> <div class="c-header__container"> <div class="c-header__split"> <div class="c-header__logo-container"> <a href="/nbt" data-track="click" data-track-action="home" data-track-label="image"> <picture class="c-header__logo"> <source srcset="https://media.springernature.com/full/nature-cms/uploads/product/nbt/header-a6bd3dd1eeb5a9d6dcc36be30996a59f.svg" media="(min-width: 875px)"> <img src="https://media.springernature.com/full/nature-cms/uploads/product/nbt/header-8f661e82c86879a1b8f03cbd053d5155.svg" height="32" alt="Nature Biotechnology"> </picture> </a> </div> <ul class="c-header__menu c-header__menu--global"> <li class="c-header__item c-header__item--padding c-header__item--hide-md-max"> <a class="c-header__link" href="https://www.nature.com/siteindex" data-test="siteindex-link" data-track="click" data-track-action="open nature research index" data-track-label="link"> <span>View all journals</span> </a> </li> <li class="c-header__item c-header__item--padding c-header__item--pipe"> <a class="c-header__link c-header__link--search" href="#search-menu" data-header-expander data-test="search-link" data-track="click" data-track-action="open search tray" data-track-label="button"> <svg role="img" aria-hidden="true" focusable="false" height="22" width="22" viewBox="0 0 18 18" xmlns="http://www.w3.org/2000/svg"><path d="M16.48 15.455c.283.282.29.749.007 1.032a.738.738 0 01-1.032-.007l-3.045-3.044a7 7 0 111.026-1.026zM8 14A6 6 0 108 2a6 6 0 000 12z"/></svg><span>Search</span> </a> </li> <li class="c-header__item c-header__item--padding c-header__item--snid-account-widget c-header__item--pipe"> <a class="c-header__link eds-c-header__link" id="identity-account-widget" data-track="click_login" data-track-context="header" href='https://idp.nature.com/auth/personal/springernature?redirect_uri=https://www.nature.com/articles/s41587-025-02570-7?error=cookies_not_supported&code=ca004362-5a33-4a20-b7b1-da2e0b21cb76'><span class="eds-c-header__widget-fragment-title">Log in</span></a> </li> </ul> </div> </div> </div> <div class="c-header__row"> <div class="c-header__container" data-test="navigation-row"> <div class="c-header__split"> <ul class="c-header__menu c-header__menu--journal"> <li class="c-header__item c-header__item--dropdown-menu" data-test="explore-content-button"> <a href="#explore" class="c-header__link" data-header-expander data-test="menu-button--explore" data-track="click" data-track-action="open explore expander" data-track-label="button"> <span><span class="c-header__show-text">Explore</span> content</span><svg role="img" aria-hidden="true" focusable="false" height="16" viewBox="0 0 16 16" width="16" xmlns="http://www.w3.org/2000/svg"><path d="m5.58578644 3-3.29289322-3.29289322c-.39052429-.39052429-.39052429-1.02368927 0-1.41421356s1.02368927-.39052429 1.41421356 0l4 4c.39052429.39052429.39052429 1.02368927 0 1.41421356l-4 4c-.39052429.39052429-1.02368927.39052429-1.41421356 0s-.39052429-1.02368927 0-1.41421356z" transform="matrix(0 1 -1 0 11 3)"/></svg> </a> </li> <li class="c-header__item c-header__item--dropdown-menu"> <a href="#about-the-journal" class="c-header__link" data-header-expander data-test="menu-button--about-the-journal" data-track="click" data-track-action="open about the journal expander" data-track-label="button"> <span>About <span class="c-header__show-text">the journal</span></span><svg role="img" aria-hidden="true" focusable="false" height="16" viewBox="0 0 16 16" width="16" xmlns="http://www.w3.org/2000/svg"><path d="m5.58578644 3-3.29289322-3.29289322c-.39052429-.39052429-.39052429-1.02368927 0-1.41421356s1.02368927-.39052429 1.41421356 0l4 4c.39052429.39052429.39052429 1.02368927 0 1.41421356l-4 4c-.39052429.39052429-1.02368927.39052429-1.41421356 0s-.39052429-1.02368927 0-1.41421356z" transform="matrix(0 1 -1 0 11 3)"/></svg> </a> </li> <li class="c-header__item c-header__item--dropdown-menu" data-test="publish-with-us-button"> <a href="#publish-with-us" class="c-header__link c-header__link--dropdown-menu" data-header-expander data-test="menu-button--publish" data-track="click" data-track-action="open publish with us expander" data-track-label="button"> <span>Publish <span class="c-header__show-text">with us</span></span><svg role="img" aria-hidden="true" focusable="false" height="16" viewBox="0 0 16 16" width="16" xmlns="http://www.w3.org/2000/svg"><path d="m5.58578644 3-3.29289322-3.29289322c-.39052429-.39052429-.39052429-1.02368927 0-1.41421356s1.02368927-.39052429 1.41421356 0l4 4c.39052429.39052429.39052429 1.02368927 0 1.41421356l-4 4c-.39052429.39052429-1.02368927.39052429-1.41421356 0s-.39052429-1.02368927 0-1.41421356z" transform="matrix(0 1 -1 0 11 3)"/></svg> </a> </li> <li class="c-header__item c-header__item--pipe c-header__item--hide-lg-max"> <a class="c-header__link" href="/nbt/subscribe" data-track="click" data-track-action="subscribe" data-track-label="link" data-test="menu-button-subscribe"> <span>Subscribe</span> </a> </li> </ul> <ul class="c-header__menu c-header__menu--hide-lg-max"> <li class="c-header__item"> <a class="c-header__link" href="https://idp.nature.com/auth/personal/springernature?redirect_uri=https%3A%2F%2Fwww.nature.com%2Fmy-account%2Falerts%2Fsubscribe-journal%3Flist-id%3D2%26journal-link%3Dhttps%253A%252F%252Fwww.nature.com%252Fnbt%252F" rel="nofollow" data-track="click" data-track-action="Sign up for alerts" data-track-label="link (desktop site header)" data-track-external> <span>Sign up for alerts</span><svg role="img" aria-hidden="true" focusable="false" height="18" viewBox="0 0 18 18" width="18" xmlns="http://www.w3.org/2000/svg"><path d="m4 10h2.5c.27614237 0 .5.2238576.5.5s-.22385763.5-.5.5h-3.08578644l-1.12132034 1.1213203c-.18753638.1875364-.29289322.4418903-.29289322.7071068v.1715729h14v-.1715729c0-.2652165-.1053568-.5195704-.2928932-.7071068l-1.7071068-1.7071067v-3.4142136c0-2.76142375-2.2385763-5-5-5-2.76142375 0-5 2.23857625-5 5zm3 4c0 1.1045695.8954305 2 2 2s2-.8954305 2-2zm-5 0c-.55228475 0-1-.4477153-1-1v-.1715729c0-.530433.21071368-1.0391408.58578644-1.4142135l1.41421356-1.4142136v-3c0-3.3137085 2.6862915-6 6-6s6 2.6862915 6 6v3l1.4142136 1.4142136c.3750727.3750727.5857864.8837805.5857864 1.4142135v.1715729c0 .5522847-.4477153 1-1 1h-4c0 1.6568542-1.3431458 3-3 3-1.65685425 0-3-1.3431458-3-3z" fill="#222"/></svg> </a> </li> <li class="c-header__item c-header__item--pipe"> <a class="c-header__link" href="https://www.nature.com/nbt.rss" data-track="click" data-track-action="rss feed" data-track-label="link"> <span>RSS feed</span> </a> </li> </ul> </div> </div> </div> </header> <nav class="u-mb-16" aria-label="breadcrumbs"> <div class="u-container"> <ol class="c-breadcrumbs" itemscope itemtype="https://schema.org/BreadcrumbList"> <li class="c-breadcrumbs__item" id="breadcrumb0" itemprop="itemListElement" itemscope itemtype="https://schema.org/ListItem"><a class="c-breadcrumbs__link" href="/" itemprop="item" data-track="click" data-track-action="breadcrumb" data-track-category="header" data-track-label="link:nature"><span itemprop="name">nature</span></a><meta itemprop="position" content="1"> <svg class="c-breadcrumbs__chevron" role="img" aria-hidden="true" focusable="false" height="10" viewBox="0 0 10 10" width="10" xmlns="http://www.w3.org/2000/svg"> <path d="m5.96738168 4.70639573 2.39518594-2.41447274c.37913917-.38219212.98637524-.38972225 1.35419292-.01894278.37750606.38054586.37784436.99719163-.00013556 1.37821513l-4.03074001 4.06319683c-.37758093.38062133-.98937525.38100976-1.367372-.00003075l-4.03091981-4.06337806c-.37759778-.38063832-.38381821-.99150444-.01600053-1.3622839.37750607-.38054587.98772445-.38240057 1.37006824.00302197l2.39538588 2.4146743.96295325.98624457z" fill="#666" fill-rule="evenodd" transform="matrix(0 -1 1 0 0 10)"/> </svg> </li><li class="c-breadcrumbs__item" id="breadcrumb1" itemprop="itemListElement" itemscope itemtype="https://schema.org/ListItem"><a class="c-breadcrumbs__link" href="/nbt" itemprop="item" data-track="click" data-track-action="breadcrumb" data-track-category="header" data-track-label="link:nature biotechnology"><span itemprop="name">nature biotechnology</span></a><meta itemprop="position" content="2"> <svg class="c-breadcrumbs__chevron" role="img" aria-hidden="true" focusable="false" height="10" viewBox="0 0 10 10" width="10" xmlns="http://www.w3.org/2000/svg"> <path d="m5.96738168 4.70639573 2.39518594-2.41447274c.37913917-.38219212.98637524-.38972225 1.35419292-.01894278.37750606.38054586.37784436.99719163-.00013556 1.37821513l-4.03074001 4.06319683c-.37758093.38062133-.98937525.38100976-1.367372-.00003075l-4.03091981-4.06337806c-.37759778-.38063832-.38381821-.99150444-.01600053-1.3622839.37750607-.38054587.98772445-.38240057 1.37006824.00302197l2.39538588 2.4146743.96295325.98624457z" fill="#666" fill-rule="evenodd" transform="matrix(0 -1 1 0 0 10)"/> </svg> </li><li class="c-breadcrumbs__item" id="breadcrumb2" itemprop="itemListElement" itemscope itemtype="https://schema.org/ListItem"><a class="c-breadcrumbs__link" href="/nbt/articles?type=article" itemprop="item" data-track="click" data-track-action="breadcrumb" data-track-category="header" data-track-label="link:articles"><span itemprop="name">articles</span></a><meta itemprop="position" content="3"> <svg class="c-breadcrumbs__chevron" role="img" aria-hidden="true" focusable="false" height="10" viewBox="0 0 10 10" width="10" xmlns="http://www.w3.org/2000/svg"> <path d="m5.96738168 4.70639573 2.39518594-2.41447274c.37913917-.38219212.98637524-.38972225 1.35419292-.01894278.37750606.38054586.37784436.99719163-.00013556 1.37821513l-4.03074001 4.06319683c-.37758093.38062133-.98937525.38100976-1.367372-.00003075l-4.03091981-4.06337806c-.37759778-.38063832-.38381821-.99150444-.01600053-1.3622839.37750607-.38054587.98772445-.38240057 1.37006824.00302197l2.39538588 2.4146743.96295325.98624457z" fill="#666" fill-rule="evenodd" transform="matrix(0 -1 1 0 0 10)"/> </svg> </li><li class="c-breadcrumbs__item" id="breadcrumb3" itemprop="itemListElement" itemscope itemtype="https://schema.org/ListItem"> <span itemprop="name">article</span><meta itemprop="position" content="4"></li> </ol> </div> </nav> </div> <div class="u-container u-mt-32 u-mb-32 u-clearfix" id="content" data-component="article-container" data-container-type="article"> <main class="c-article-main-column u-float-left js-main-column" data-track-component="article body"> <article lang="en"> <div class="c-article-header"> <header> <ul class="c-article-identifiers" data-test="article-identifier"> <li class="c-article-identifiers__item" data-test="article-category">Article</li> <li class="c-article-identifiers__item">Published: <time datetime="2025-02-18">18 February 2025</time></li> </ul> <h1 class="c-article-title" data-test="article-title" data-article-title="">Sustained in situ protein production and release in the mammalian gut by an engineered bacteriophage</h1> <ul class="c-article-author-list c-article-author-list--short" data-test="authors-list" data-component-authors-activator="authors-list"><li class="c-article-author-list__item"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Zachary_R_-Baker-Aff1-Aff2-Aff3" data-author-popup="auth-Zachary_R_-Baker-Aff1-Aff2-Aff3" data-author-search="Baker, Zachary R.">Zachary R. Baker</a><sup class="u-js-hide"><a href="#Aff1">1</a>,<a href="#Aff2">2</a>,<a href="#Aff3">3</a></sup>, </li><li class="c-article-author-list__item"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Yao-Zhang-Aff1" data-author-popup="auth-Yao-Zhang-Aff1" data-author-search="Zhang, Yao">Yao Zhang</a><span class="u-js-hide"> <a class="js-orcid" href="http://orcid.org/0000-0002-0943-090X"><span class="u-visually-hidden">ORCID: </span>orcid.org/0000-0002-0943-090X</a></span><sup class="u-js-hide"><a href="#Aff1">1</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Haiyan-Zhang-Aff4" data-author-popup="auth-Haiyan-Zhang-Aff4" data-author-search="Zhang, Haiyan">Haiyan Zhang</a><sup class="u-js-hide"><a href="#Aff4">4</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Hollyn_C_-Franklin-Aff1-Aff2-Aff3" data-author-popup="auth-Hollyn_C_-Franklin-Aff1-Aff2-Aff3" data-author-search="Franklin, Hollyn C.">Hollyn C. Franklin</a><sup class="u-js-hide"><a href="#Aff1">1</a>,<a href="#Aff2">2</a>,<a href="#Aff3">3</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Priscila_B__S_-Serpa-Aff5" data-author-popup="auth-Priscila_B__S_-Serpa-Aff5" data-author-search="Serpa, Priscila B. S.">Priscila B. S. Serpa</a><span class="u-js-hide"> <a class="js-orcid" href="http://orcid.org/0000-0001-6073-2172"><span class="u-visually-hidden">ORCID: </span>orcid.org/0000-0001-6073-2172</a></span><sup class="u-js-hide"><a href="#Aff5">5</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Teresa-Southard-Aff5" data-author-popup="auth-Teresa-Southard-Aff5" data-author-search="Southard, Teresa">Teresa Southard</a><sup class="u-js-hide"><a href="#Aff5">5</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Liwu-Li-Aff1" data-author-popup="auth-Liwu-Li-Aff1" data-author-search="Li, Liwu" data-corresp-id="c1">Liwu Li<svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-mail-medium"></use></svg></a><span class="u-js-hide"> <a class="js-orcid" href="http://orcid.org/0000-0001-8870-5299"><span class="u-visually-hidden">ORCID: </span>orcid.org/0000-0001-8870-5299</a></span><sup class="u-js-hide"><a href="#Aff1">1</a></sup> & </li><li class="c-article-author-list__show-more" aria-label="Show all 8 authors for this article" title="Show all 8 authors for this article">…</li><li class="c-article-author-list__item"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Bryan_B_-Hsu-Aff1-Aff2-Aff3-Aff5" data-author-popup="auth-Bryan_B_-Hsu-Aff1-Aff2-Aff3-Aff5" data-author-search="Hsu, Bryan B." data-corresp-id="c2">Bryan B. Hsu<svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-mail-medium"></use></svg></a><span class="u-js-hide"> <a class="js-orcid" href="http://orcid.org/0000-0002-8219-1124"><span class="u-visually-hidden">ORCID: </span>orcid.org/0000-0002-8219-1124</a></span><sup class="u-js-hide"><a href="#Aff1">1</a>,<a href="#Aff2">2</a>,<a href="#Aff3">3</a>,<a href="#Aff5">5</a></sup> </li></ul><button aria-expanded="false" class="c-article-author-list__button"><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-down-medium"></use></svg><span>Show authors</span></button> <p class="c-article-info-details" data-container-section="info"> <a data-test="journal-link" href="/nbt" data-track="click" data-track-action="journal homepage" data-track-category="article body" data-track-label="link"><i data-test="journal-title">Nature Biotechnology</i></a> (<span data-test="article-publication-year">2025</span>)<a href="#citeas" class="c-article-info-details__cite-as u-hide-print" data-track="click" data-track-action="cite this article" data-track-label="link">Cite this article</a> </p> <div class="c-article-metrics-bar__wrapper u-clear-both"> <ul class="c-article-metrics-bar u-list-reset"> <li class=" c-article-metrics-bar__item" data-test="access-count"> <p class="c-article-metrics-bar__count">1690 <span class="c-article-metrics-bar__label">Accesses</span></p> </li> <li class="c-article-metrics-bar__item" data-test="altmetric-score"> <p class="c-article-metrics-bar__count">100 <span class="c-article-metrics-bar__label">Altmetric</span></p> </li> <li class="c-article-metrics-bar__item"> <p class="c-article-metrics-bar__details"><a href="/articles/s41587-025-02570-7/metrics" data-track="click" data-track-action="view metrics" data-track-label="link" rel="nofollow">Metrics <span class="u-visually-hidden">details</span></a></p> </li> </ul> </div> </header> <div class="u-js-hide" data-component="article-subject-links"> <h3 class="c-article__sub-heading">Subjects</h3> <ul class="c-article-subject-list"> <li class="c-article-subject-list__subject"><a href="/subjects/applied-microbiology" data-track="click" data-track-action="view subject" data-track-label="link">Applied microbiology</a></li><li class="c-article-subject-list__subject"><a href="/subjects/bacteriophages" data-track="click" data-track-action="view subject" data-track-label="link">Bacteriophages</a></li><li class="c-article-subject-list__subject"><a href="/subjects/biotechnology" data-track="click" data-track-action="view subject" data-track-label="link">Biotechnology</a></li> </ul> </div> </div> <div class="c-article-body"> <section aria-labelledby="Abs1" data-title="Abstract" lang="en"><div class="c-article-section" id="Abs1-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Abs1">Abstract</h2><div class="c-article-section__content" id="Abs1-content"><p>Oral administration of biologic drugs is challenging because of the degradative activity of the upper gastrointestinal tract. Strategies that use engineered microbes to produce biologics in the lower gastrointestinal tract are limited by competition with resident commensal bacteria. Here we demonstrate the engineering of bacteriophage (phage) that infect resident commensals to express heterologous proteins released during cell lysis. Working with the virulent T4 phage, which targets resident, nonpathogenic <i>Escherichia coli</i>, we first identify T4-specific promoters with maximal protein expression and minimal impact on T4 phage titers. We engineer T4 phage to express a serine protease inhibitor of a pro-inflammatory enzyme with increased activity in ulcerative colitis and observe reduced enzyme activity in a mouse model of colitis. We also apply the approach to reduce weight gain and inflammation in mouse models of diet-induced obesity. This work highlights an application of virulent phages in the mammalian gut as engineerable vectors to release therapeutics from resident gut bacteria.</p></div></div></section> <noscript> <div class="c-nature-box c-nature-box--side " data-component="entitlement-box"> <div class="js-access-button"> <a href="https://wayf.springernature.com?redirect_uri=https%3A%2F%2Fwww.nature.com%2Farticles%2Fs41587-025-02570-7" class="c-article__button" data-test="ra21"> <svg class="u-icon" width="18" height="18" aria-hidden="true" focusable="false"><use href="#icon-institution"></use></svg> <span class="c-article__button-text">Access through your institution</span> </a> </div> <div class="js-buy-button"> <a href="#access-options" class="c-article__button c-article__button--inverted" data-test="ra21"> <span>Buy or subscribe</span> </a> </div> </div> </noscript> <div class="js-context-bar-sticky-point-mobile" data-track-context="article body"> </div> <div class="c-article-access-provider u-mb-32 u-mt-0"> <p class="c-article-access-provider__text u-sans-serif">This is a preview of subscription content, <a href="https://wayf.springernature.com?redirect_uri=https%3A%2F%2Fwww.nature.com%2Farticles%2Fs41587-025-02570-7" data-track="click_institution_login" data-track-context="article body link" data-track-action="institution access preview subscription" data-track-label="link">access via your institution</a></p> </div> <h2 class="c-article-section__title u-h2 u-mb-24" id="access-options">Access options</h2> <noscript> <div class="c-nature-box c-nature-box--side " data-component="entitlement-box"> <div class="js-access-button"> <a href="https://wayf.springernature.com?redirect_uri=https%3A%2F%2Fwww.nature.com%2Farticles%2Fs41587-025-02570-7" class="c-article__button" data-test="ra21"> <svg class="u-icon" width="18" height="18" aria-hidden="true" focusable="false"><use href="#icon-institution"></use></svg> <span class="c-article__button-text">Access through your institution</span> </a> </div> </div> </noscript> <div class="c-nature-box c-nature-box--side u-display-none u-hide-print" aria-hidden="true" data-component="entitlement-box" id=entitlement-box-main-column-unentitled data-force-hide-buy-button="true" data-unsubscribe-media-query-change="true" > <p class="c-nature-box__text js-text u-display-none" aria-hidden="true"></p> <div class="js-access-button u-display-none"> <a href="https://wayf.springernature.com?redirect_uri=https%3A%2F%2Fwww.nature.com%2Farticles%2Fs41587-025-02570-7" class="c-article__button" aria-hidden="true" data-test="ra21" data-track="click_institution_login" data-track-context="article body button" data-track-action="institution access above buybox" data-track-label="button"> <svg class="u-icon" width="18" height="18" aria-hidden="true" focusable="false"><use xlink:href="#icon-institution"></use></svg> <span class="c-article__button-text">Access through your institution</span> </a> </div> <div class="js-change-institution-button u-display-none"> <a href="https://wayf.springernature.com?redirect_uri=https%3A%2F%2Fwww.nature.com%2Farticles%2Fs41587-025-02570-7" class="c-article__button c-article__button--inverted" aria-hidden="true" data-test="ra21" data-track="click" data-track-action="change institution above buybox" data-track-label="button"> <span class="c-article__button-text">Change institution</span> </a> </div> <div class="js-buy-button u-display-none"> <a href="#access-options" class="c-article__button c-article__button--inverted" aria-hidden="true" data-test="ra21" data-track="click" data-track-action="buy or subscribe" data-track-label="button"> <span>Buy or subscribe</span> </a> </div> </div> <div class="LiveAreaSection"><style type="text/css">/* style specs start */ /* style specs end */</style><section class="BuyBoxSection"><div class="subscribe-buybox-nature-plus"> <div class="box-inner"> <p class="title-buybox"> Access Nature and 54 other Nature Portfolio journals </p> <p class="access-buybox"> Get Nature+, our best-value online-access subscription </p> <div> <p class="price-buybox" id="nature-plus-subscription-price"> <span class="price-value">24,99 €<span class="price-per-period" style="font-size: 0.9rem"> / 30 days</span></span> </p> <p class="issue-buybox">cancel any time</p> </div> <div class="button-container"> <a href="https://shop.nature.com/products/plus" class="Button-505204839" data-track="click" data-track-action="nature+" data-track-label="link" data-track-category="article body" ><span class="ButtonLabel-3869432492">Learn more</span></a > </div> </div> </div><div class="subscribe-buybox"> <div class="box-inner"> <p class="title-buybox">Subscribe to this journal</p> <p class="access-buybox"> Receive 12 print issues and online access </p> <div> <p class="price-buybox" id="subscription-price">195,33 € per year</p> <p class="issue-buybox">only 16,28 € per issue</p> </div> <div class="button-container"> <a href="/nbt/subscribe" class="Button-1078489254" data-track="click" data-track-action="subscribe" data-track-label="link" data-track-category="article body" ><span class="ButtonLabel-3296148077">Learn more</span></a > </div> </div> </div><div class="readcube-buybox"> <div class="box-inner"> <p class="title-readcube">Buy this article</p> <ul> <li class="link-usp"><span>Purchase on SpringerLink</span></li> <li class="link-usp"> <span>Instant access to full article PDF</span> </li> </ul> <div class="button-container"> <a href="//link.springer.com/article/10.1038/s41587-025-02570-7?utm_source=nature&utm_medium=referral&utm_campaign=buyArticle" class="btn-secondary Button-2737859108" data-track="click" data-track-action="Go to SL article page" data-track-label="link" data-track-category="article body" rel="noreferrer" ><span class="btn-secondary-label ButtonLabel-1636778223" >Buy now</span ></a > </div> </div> </div><p class="tax-buybox">Prices may be subject to local taxes which are calculated during checkout</p></section><style type="text/css"> /* style specs start */ style { display: none !important; } .LiveAreaSection * { align-content: stretch; align-items: stretch; align-self: auto; animation-delay: 0s; animation-direction: normal; animation-duration: 0s; animation-fill-mode: none; animation-iteration-count: 1; animation-name: none; animation-play-state: running; animation-timing-function: ease; azimuth: center; backface-visibility: visible; background-attachment: scroll; background-blend-mode: normal; background-clip: borderBox; background-color: transparent; background-image: none; background-origin: paddingBox; background-position: 0 0; background-repeat: repeat; background-size: auto auto; block-size: auto; border-block-end-color: currentcolor; border-block-end-style: none; border-block-end-width: medium; border-block-start-color: currentcolor; border-block-start-style: none; border-block-start-width: medium; border-bottom-color: currentcolor; border-bottom-left-radius: 0; border-bottom-right-radius: 0; border-bottom-style: none; border-bottom-width: medium; border-collapse: separate; border-image-outset: 0s; border-image-repeat: stretch; border-image-slice: 100%; border-image-source: none; border-image-width: 1; border-inline-end-color: currentcolor; border-inline-end-style: none; border-inline-end-width: medium; border-inline-start-color: currentcolor; border-inline-start-style: none; border-inline-start-width: medium; border-left-color: currentcolor; border-left-style: none; border-left-width: medium; border-right-color: currentcolor; border-right-style: none; border-right-width: medium; border-spacing: 0; border-top-color: currentcolor; border-top-left-radius: 0; border-top-right-radius: 0; border-top-style: none; border-top-width: medium; bottom: auto; box-decoration-break: slice; box-shadow: none; box-sizing: border-box; break-after: auto; break-before: auto; break-inside: auto; caption-side: top; caret-color: auto; clear: none; clip: auto; clip-path: none; color: initial; column-count: auto; column-fill: balance; column-gap: normal; column-rule-color: currentcolor; column-rule-style: none; column-rule-width: medium; column-span: none; column-width: auto; content: normal; counter-increment: none; counter-reset: none; cursor: auto; display: inline; empty-cells: show; filter: none; flex-basis: auto; flex-direction: row; flex-grow: 0; flex-shrink: 1; flex-wrap: nowrap; float: none; font-family: initial; font-feature-settings: normal; font-kerning: auto; font-language-override: normal; font-size: medium; font-size-adjust: none; font-stretch: normal; font-style: normal; font-synthesis: weight style; font-variant: normal; font-variant-alternates: normal; font-variant-caps: normal; font-variant-east-asian: normal; font-variant-ligatures: normal; font-variant-numeric: normal; font-variant-position: normal; font-weight: 400; grid-auto-columns: auto; grid-auto-flow: row; grid-auto-rows: auto; grid-column-end: auto; grid-column-gap: 0; grid-column-start: auto; grid-row-end: auto; grid-row-gap: 0; grid-row-start: auto; grid-template-areas: none; grid-template-columns: none; grid-template-rows: none; height: auto; hyphens: manual; image-orientation: 0deg; image-rendering: auto; image-resolution: 1dppx; ime-mode: auto; inline-size: auto; isolation: auto; justify-content: flexStart; left: auto; letter-spacing: normal; line-break: auto; line-height: normal; list-style-image: none; list-style-position: outside; list-style-type: disc; margin-block-end: 0; margin-block-start: 0; margin-bottom: 0; margin-inline-end: 0; margin-inline-start: 0; margin-left: 0; margin-right: 0; margin-top: 0; mask-clip: borderBox; mask-composite: add; mask-image: none; mask-mode: matchSource; mask-origin: borderBox; mask-position: 0 0; mask-repeat: repeat; mask-size: auto; mask-type: luminance; max-height: none; max-width: none; min-block-size: 0; min-height: 0; min-inline-size: 0; min-width: 0; mix-blend-mode: normal; object-fit: fill; object-position: 50% 50%; offset-block-end: auto; offset-block-start: auto; offset-inline-end: auto; offset-inline-start: auto; opacity: 1; order: 0; orphans: 2; outline-color: initial; outline-offset: 0; outline-style: none; outline-width: medium; overflow: visible; overflow-wrap: normal; overflow-x: visible; overflow-y: visible; padding-block-end: 0; padding-block-start: 0; padding-bottom: 0; padding-inline-end: 0; padding-inline-start: 0; padding-left: 0; padding-right: 0; padding-top: 0; page-break-after: auto; page-break-before: auto; page-break-inside: auto; perspective: none; perspective-origin: 50% 50%; pointer-events: auto; position: static; quotes: initial; resize: none; right: auto; ruby-align: spaceAround; ruby-merge: separate; ruby-position: over; scroll-behavior: auto; scroll-snap-coordinate: none; scroll-snap-destination: 0 0; scroll-snap-points-x: none; scroll-snap-points-y: none; scroll-snap-type: none; shape-image-threshold: 0; shape-margin: 0; shape-outside: none; tab-size: 8; table-layout: auto; text-align: initial; text-align-last: auto; text-combine-upright: none; text-decoration-color: currentcolor; text-decoration-line: none; text-decoration-style: solid; text-emphasis-color: currentcolor; text-emphasis-position: over right; text-emphasis-style: none; text-indent: 0; text-justify: auto; text-orientation: mixed; text-overflow: clip; text-rendering: auto; text-shadow: none; text-transform: none; text-underline-position: auto; top: auto; touch-action: auto; transform: none; transform-box: borderBox; transform-origin: 50% 50%0; transform-style: flat; transition-delay: 0s; transition-duration: 0s; transition-property: all; transition-timing-function: ease; vertical-align: baseline; visibility: visible; white-space: normal; widows: 2; width: auto; will-change: auto; word-break: normal; word-spacing: normal; word-wrap: normal; writing-mode: horizontalTb; z-index: auto; -webkit-appearance: none; -moz-appearance: none; -ms-appearance: none; appearance: none; margin: 0; } .LiveAreaSection { width: 100%; } .LiveAreaSection .login-option-buybox { display: block; width: 100%; font-size: 17px; line-height: 30px; color: #222; padding-top: 30px; font-family: Harding, Palatino, serif; } .LiveAreaSection .additional-access-options { display: block; font-weight: 700; font-size: 17px; line-height: 30px; color: #222; font-family: Harding, Palatino, serif; } .LiveAreaSection .additional-login > li:not(:first-child)::before { transform: translateY(-50%); content: ""; height: 1rem; position: absolute; top: 50%; left: 0; border-left: 2px solid #999; } .LiveAreaSection .additional-login > li:not(:first-child) { padding-left: 10px; } .LiveAreaSection .additional-login > li { display: inline-block; position: relative; vertical-align: middle; padding-right: 10px; } .BuyBoxSection { display: flex; flex-wrap: wrap; flex: 1; flex-direction: row-reverse; margin: -30px -15px 0; } .BuyBoxSection .box-inner { width: 100%; height: 100%; padding: 30px 5px; display: flex; flex-direction: column; justify-content: space-between; } .BuyBoxSection p { margin: 0; } .BuyBoxSection .readcube-buybox { background-color: #f3f3f3; flex-shrink: 1; flex-grow: 1; flex-basis: 255px; background-clip: content-box; padding: 0 15px; margin-top: 30px; } .BuyBoxSection .subscribe-buybox { background-color: #f3f3f3; flex-shrink: 1; flex-grow: 4; flex-basis: 300px; background-clip: content-box; padding: 0 15px; margin-top: 30px; } .BuyBoxSection .subscribe-buybox-nature-plus { background-color: #f3f3f3; flex-shrink: 1; flex-grow: 4; flex-basis: 100%; background-clip: content-box; padding: 0 15px; margin-top: 30px; } .BuyBoxSection .title-readcube, .BuyBoxSection .title-buybox { display: block; margin: 0; margin-right: 10%; margin-left: 10%; font-size: 24px; line-height: 32px; color: #222; text-align: center; font-family: Harding, Palatino, serif; } .BuyBoxSection .title-asia-buybox { display: block; margin: 0; margin-right: 5%; margin-left: 5%; font-size: 24px; line-height: 32px; color: #222; text-align: center; font-family: Harding, Palatino, serif; } .BuyBoxSection .asia-link, .Link-328123652, .Link-2926870917, .Link-2291679238, .Link-595459207 { color: #069; cursor: pointer; text-decoration: none; font-size: 1.05em; font-family: -apple-system, BlinkMacSystemFont, "Segoe UI", Roboto, Oxygen-Sans, Ubuntu, Cantarell, "Helvetica Neue", sans-serif; line-height: 1.05em6; } .BuyBoxSection .access-readcube { display: block; margin: 0; margin-right: 10%; margin-left: 10%; font-size: 14px; color: #222; padding-top: 10px; text-align: center; font-family: -apple-system, BlinkMacSystemFont, "Segoe UI", Roboto, Oxygen-Sans, Ubuntu, Cantarell, "Helvetica Neue", sans-serif; line-height: 20px; } .BuyBoxSection ul { margin: 0; } .BuyBoxSection .link-usp { display: list-item; margin: 0; margin-left: 20px; padding-top: 6px; list-style-position: inside; } .BuyBoxSection .link-usp span { font-size: 14px; color: #222; font-family: -apple-system, BlinkMacSystemFont, "Segoe UI", Roboto, Oxygen-Sans, Ubuntu, Cantarell, "Helvetica Neue", sans-serif; line-height: 20px; } .BuyBoxSection .access-asia-buybox { display: block; margin: 0; margin-right: 5%; margin-left: 5%; font-size: 14px; color: #222; padding-top: 10px; text-align: center; font-family: -apple-system, BlinkMacSystemFont, "Segoe UI", Roboto, Oxygen-Sans, Ubuntu, Cantarell, "Helvetica Neue", sans-serif; line-height: 20px; } .BuyBoxSection .access-buybox { display: block; margin: 0; margin-right: 10%; margin-left: 10%; font-size: 14px; color: #222; opacity: 0.8px; padding-top: 10px; text-align: center; font-family: -apple-system, BlinkMacSystemFont, "Segoe UI", Roboto, Oxygen-Sans, Ubuntu, Cantarell, "Helvetica Neue", sans-serif; line-height: 20px; } .BuyBoxSection .price-buybox { display: block; font-size: 30px; color: #222; font-family: -apple-system, BlinkMacSystemFont, "Segoe UI", Roboto, Oxygen-Sans, Ubuntu, Cantarell, "Helvetica Neue", sans-serif; padding-top: 30px; text-align: center; } .BuyBoxSection .price-buybox-to { display: block; font-size: 30px; color: #222; font-family: -apple-system, BlinkMacSystemFont, "Segoe UI", Roboto, Oxygen-Sans, Ubuntu, Cantarell, "Helvetica Neue", sans-serif; text-align: center; } .BuyBoxSection .price-info-text { font-size: 16px; padding-right: 10px; color: #222; font-family: -apple-system, BlinkMacSystemFont, "Segoe UI", Roboto, Oxygen-Sans, Ubuntu, Cantarell, "Helvetica Neue", sans-serif; } .BuyBoxSection .price-value { font-size: 30px; font-family: -apple-system, BlinkMacSystemFont, "Segoe UI", Roboto, Oxygen-Sans, Ubuntu, Cantarell, "Helvetica Neue", sans-serif; } .BuyBoxSection .price-per-period { font-family: -apple-system, BlinkMacSystemFont, "Segoe UI", Roboto, Oxygen-Sans, Ubuntu, Cantarell, "Helvetica Neue", sans-serif; } .BuyBoxSection .price-from { font-size: 14px; padding-right: 10px; color: #222; font-family: -apple-system, BlinkMacSystemFont, "Segoe UI", Roboto, Oxygen-Sans, Ubuntu, Cantarell, "Helvetica Neue", sans-serif; line-height: 20px; } .BuyBoxSection .issue-buybox { display: block; font-size: 13px; text-align: center; color: #222; font-family: -apple-system, BlinkMacSystemFont, "Segoe UI", Roboto, Oxygen-Sans, Ubuntu, Cantarell, "Helvetica Neue", sans-serif; line-height: 19px; } .BuyBoxSection .no-price-buybox { display: block; font-size: 13px; line-height: 18px; text-align: center; padding-right: 10%; padding-left: 10%; padding-bottom: 20px; padding-top: 30px; color: #222; font-family: -apple-system, BlinkMacSystemFont, "Segoe UI", Roboto, Oxygen-Sans, Ubuntu, Cantarell, "Helvetica Neue", sans-serif; } .BuyBoxSection .vat-buybox { display: block; margin-top: 5px; margin-right: 20%; margin-left: 20%; font-size: 11px; color: #222; padding-top: 10px; padding-bottom: 15px; text-align: center; font-family: -apple-system, BlinkMacSystemFont, "Segoe UI", Roboto, Oxygen-Sans, Ubuntu, Cantarell, "Helvetica Neue", sans-serif; line-height: 17px; } .BuyBoxSection .tax-buybox { display: block; width: 100%; color: #222; padding: 20px 16px; text-align: center; font-family: -apple-system, BlinkMacSystemFont, "Segoe UI", Roboto, Oxygen-Sans, Ubuntu, Cantarell, "Helvetica Neue", sans-serif; line-height: NaNpx; } .BuyBoxSection .button-container { display: flex; padding-right: 20px; padding-left: 20px; justify-content: center; } .BuyBoxSection .button-container > * { flex: 1px; } .BuyBoxSection .button-container > a:hover, .Button-505204839:hover, .Button-1078489254:hover, .Button-2737859108:hover { text-decoration: none; } .BuyBoxSection .btn-secondary { background: #fff; } .BuyBoxSection .button-asia { background: #069; border: 1px solid #069; border-radius: 0; cursor: pointer; display: block; padding: 9px; outline: 0; text-align: center; text-decoration: none; min-width: 80px; margin-top: 75px; } .BuyBoxSection .button-label-asia, .ButtonLabel-3869432492, .ButtonLabel-3296148077, .ButtonLabel-1636778223 { display: block; color: #fff; font-size: 17px; line-height: 20px; font-family: -apple-system, BlinkMacSystemFont, "Segoe UI", Roboto, Oxygen-Sans, Ubuntu, Cantarell, "Helvetica Neue", sans-serif; text-align: center; text-decoration: none; cursor: pointer; } .Button-505204839, .Button-1078489254, .Button-2737859108 { background: #069; border: 1px solid #069; border-radius: 0; cursor: pointer; display: block; padding: 9px; outline: 0; text-align: center; text-decoration: none; min-width: 80px; max-width: 320px; margin-top: 20px; } .Button-505204839 .btn-secondary-label, .Button-1078489254 .btn-secondary-label, .Button-2737859108 .btn-secondary-label { color: #069; } .uList-2102244549 { list-style: none; padding: 0; margin: 0; } /* style specs end */</style><div></div></div> <nav class="c-access-options"> <h3 class="c-access-options__heading">Additional access options:</h3> <ul class="c-access-options__list"> <li> <a href="https://idp.nature.com/authorize/natureuser?client_id=grover&redirect_uri=https%3A%2F%2Fwww.nature.com%2Farticles%2Fs41587-025-02570-7" data-track="click" data-track-action="login" data-track-category="article body" data-track-label="link">Log in</a> </li> <li> <a href="https://www.springernature.com/gp/librarians/licensing/license-options" data-track="click" data-track-action="learn-subscription" data-track-category="article body" data-track-label="link">Learn about institutional subscriptions</a> </li> <li> <a href="https://support.nature.com/en/support/home" data-track="click" data-track-action="read our faqs" data-track-category="article body" data-track-label="link">Read our FAQs</a> </li> <li> <a href="https://www.springernature.com/gp/contact" data-track="click" data-track-action="contact customer support" data-track-category="article body" data-track-label="link">Contact customer support</a> </li> </ul> </nav> <div class="u-display-none"> <div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-1"><figure><figcaption><b id="Fig1" class="c-article-section__figure-caption" data-test="figure-caption-text">Fig. 1: Phage-induced lysis of bacteria releases intracellular proteins.</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><picture><source type="image/webp" srcset="//media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fs41587-025-02570-7/MediaObjects/41587_2025_2570_Fig1_HTML.png?as=webp"><img src="//media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fs41587-025-02570-7/MediaObjects/41587_2025_2570_Fig1_HTML.png" alt="" loading="lazy" width="286" height="312"></picture></div></div></figure></div><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-2"><figure><figcaption><b id="Fig2" class="c-article-section__figure-caption" data-test="figure-caption-text">Fig. 2: Survey of T4 phage promoters for in vitro sfGFP production.</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><picture><source type="image/webp" srcset="//media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fs41587-025-02570-7/MediaObjects/41587_2025_2570_Fig2_HTML.png?as=webp"><img src="//media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fs41587-025-02570-7/MediaObjects/41587_2025_2570_Fig2_HTML.png" alt="" loading="lazy" width="312" height="100"></picture></div></div></figure></div><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-3"><figure><figcaption><b id="Fig3" class="c-article-section__figure-caption" data-test="figure-caption-text">Fig. 3: In vivo sfGFP production by engineered phage.</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><picture><source type="image/webp" srcset="//media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fs41587-025-02570-7/MediaObjects/41587_2025_2570_Fig3_HTML.png?as=webp"><img src="//media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fs41587-025-02570-7/MediaObjects/41587_2025_2570_Fig3_HTML.png" alt="" loading="lazy" width="228" height="312"></picture></div></div></figure></div><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-4"><figure><figcaption><b id="Fig4" class="c-article-section__figure-caption" data-test="figure-caption-text">Fig. 4: Reduction of DSS-induced colitis via Serpin production.</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><picture><source type="image/webp" srcset="//media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fs41587-025-02570-7/MediaObjects/41587_2025_2570_Fig4_HTML.png?as=webp"><img src="//media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fs41587-025-02570-7/MediaObjects/41587_2025_2570_Fig4_HTML.png" alt="" loading="lazy" width="303" height="312"></picture></div></div></figure></div><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-5"><figure><figcaption><b id="Fig5" class="c-article-section__figure-caption" data-test="figure-caption-text">Fig. 5: The efficacy of T4::<i>clpB</i> to reduce food consumption and weight gain.</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><picture><source type="image/webp" srcset="//media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fs41587-025-02570-7/MediaObjects/41587_2025_2570_Fig5_HTML.png?as=webp"><img src="//media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fs41587-025-02570-7/MediaObjects/41587_2025_2570_Fig5_HTML.png" alt="" loading="lazy" width="172" height="312"></picture></div></div></figure></div> </div> <section aria-labelledby="inline-recommendations" data-title="Inline Recommendations" class="c-article-recommendations" data-track-component="inline-recommendations"> <h3 class="c-article-recommendations-title" id="inline-recommendations">Similar content being viewed by others</h3> <div class="c-article-recommendations-list"> <div class="c-article-recommendations-list__item"> <article class="c-article-recommendations-card" itemscope itemtype="http://schema.org/ScholarlyArticle"> <div class="c-article-recommendations-card__img"><img src="https://media.springernature.com/w215h120/springer-static/image/art%3A10.1038%2Fs41575-021-00536-z/MediaObjects/41575_2021_536_Fig1_HTML.png" loading="lazy" alt=""></div> <div class="c-article-recommendations-card__main"> <h3 class="c-article-recommendations-card__heading" itemprop="name headline"> <a class="c-article-recommendations-card__link" itemprop="url" href="https://www.nature.com/articles/s41575-021-00536-z?fromPaywallRec=true" data-track="select_recommendations_1" data-track-context="inline recommendations" data-track-action="click recommendations inline - 1" data-track-label="10.1038/s41575-021-00536-z">Bacteriophages and their potential for treatment of gastrointestinal diseases </a> </h3> <div class="c-article-meta-recommendations" data-test="recommendation-info"> <span class="c-article-meta-recommendations__item-type">Article</span> <span class="c-article-meta-recommendations__date">15 November 2021</span> </div> </div> </article> </div> <div class="c-article-recommendations-list__item"> <article class="c-article-recommendations-card" itemscope itemtype="http://schema.org/ScholarlyArticle"> <div class="c-article-recommendations-card__img"><img src="https://media.springernature.com/w215h120/springer-static/image/art%3A10.1038%2Fs41467-020-18614-2/MediaObjects/41467_2020_18614_Fig1_HTML.png" loading="lazy" alt=""></div> <div class="c-article-recommendations-card__main"> <h3 class="c-article-recommendations-card__heading" itemprop="name headline"> <a class="c-article-recommendations-card__link" itemprop="url" href="https://www.nature.com/articles/s41467-020-18614-2?fromPaywallRec=true" data-track="select_recommendations_2" data-track-context="inline recommendations" data-track-action="click recommendations inline - 2" data-track-label="10.1038/s41467-020-18614-2">In situ reprogramming of gut bacteria by oral delivery </a> </h3> <div class="c-article-meta-recommendations" data-test="recommendation-info"> <span class="c-article-meta-recommendations__item-type">Article</span> <span class="c-article-meta-recommendations__access-type">Open access</span> <span class="c-article-meta-recommendations__date">06 October 2020</span> </div> </div> </article> </div> <div class="c-article-recommendations-list__item"> <article class="c-article-recommendations-card" itemscope itemtype="http://schema.org/ScholarlyArticle"> <div class="c-article-recommendations-card__img"><img src="https://media.springernature.com/w215h120/springer-static/image/art%3A10.1038%2Fs41551-020-0556-3/MediaObjects/41551_2020_556_Fig1_HTML.png" loading="lazy" alt=""></div> <div class="c-article-recommendations-card__main"> <h3 class="c-article-recommendations-card__heading" itemprop="name headline"> <a class="c-article-recommendations-card__link" itemprop="url" href="https://www.nature.com/articles/s41551-020-0556-3?fromPaywallRec=true" data-track="select_recommendations_3" data-track-context="inline recommendations" data-track-action="click recommendations inline - 3" data-track-label="10.1038/s41551-020-0556-3">De novo development of proteolytically resistant therapeutic peptides for oral administration </a> </h3> <div class="c-article-meta-recommendations" data-test="recommendation-info"> <span class="c-article-meta-recommendations__item-type">Article</span> <span class="c-article-meta-recommendations__date">11 May 2020</span> </div> </div> </article> </div> </div> </section> <script> window.dataLayer = window.dataLayer || []; window.dataLayer.push({ recommendations: { recommender: 'semantic', model: 'specter', policy_id: 'NA', timestamp: 1740146199, embedded_user: 'null' } }); </script> <div class="u-mt-32"> <section data-title="Data availability"><div class="c-article-section" id="data-availability-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="data-availability">Data availability</h2><div class="c-article-section__content" id="data-availability-content"> <p>Source data for figures in the main text and <a data-track="click" data-track-label="link" data-track-action="section anchor" href="/articles/s41587-025-02570-7#Sec18">Supplementary Information</a> are provided with this paper. 16S amplicon reads are available on Mendeley Data<sup><a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 85" title="Baker, Z. 16S Illumina sequencing reads. Mendeley Data 
 data.mendeley.com/datasets/pt9m6b9s4z/1
 
 (2024)." href="/articles/s41587-025-02570-7#ref-CR85" id="ref-link-section-d11902627e2702">85</a></sup>. <a data-track="click" data-track-label="link" data-track-action="section anchor" href="/articles/s41587-025-02570-7#Sec19">Source data</a> are provided with this paper.</p> </div></div></section><section data-title="Code availability"><div class="c-article-section" id="code-availability-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="code-availability">Code availability</h2><div class="c-article-section__content" id="code-availability-content"> <p>No code was generated in this study.</p> </div></div></section><div id="MagazineFulltextArticleBodySuffix"><section aria-labelledby="Bib1" data-title="References"><div class="c-article-section" id="Bib1-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Bib1">References</h2><div class="c-article-section__content" id="Bib1-content"><div data-container-section="references"><ol class="c-article-references" data-track-component="outbound reference" data-track-context="references section"><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="1."><p class="c-article-references__text" id="ref-CR1">Hua, S. Advances in oral drug delivery for regional targeting in the gastrointestinal tract—influence of physiological, pathophysiological and pharmaceutical factors. <i>Front. Pharmacol.</i> <b>11</b>, 524 (2020).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.3389/fphar.2020.00524" data-track-item_id="10.3389/fphar.2020.00524" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.3389%2Ffphar.2020.00524" aria-label="Article reference 1" data-doi="10.3389/fphar.2020.00524">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BB3cXhvFKktbfP" aria-label="CAS reference 1">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=32425781" aria-label="PubMed reference 1">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212533" aria-label="PubMed Central reference 1">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 1" href="http://scholar.google.com/scholar_lookup?&title=Advances%20in%20oral%20drug%20delivery%20for%20regional%20targeting%20in%20the%20gastrointestinal%20tract%E2%80%94influence%20of%20physiological%2C%20pathophysiological%20and%20pharmaceutical%20factors&journal=Front.%20Pharmacol.&doi=10.3389%2Ffphar.2020.00524&volume=11&publication_year=2020&author=Hua%2CS"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="2."><p class="c-article-references__text" id="ref-CR2">Tripathi, J., Thapa, P., Maharjan, R. & Jeong, S. H. Currentstate and future perspectives on gastroretentive drug delivery systems. <i>Pharmaceutics</i> <b>11</b>, 193 (2019).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.3390/pharmaceutics11040193" data-track-item_id="10.3390/pharmaceutics11040193" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.3390%2Fpharmaceutics11040193" aria-label="Article reference 2" data-doi="10.3390/pharmaceutics11040193">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC1MXisVSrtL3P" aria-label="CAS reference 2">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=31010054" aria-label="PubMed reference 2">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6523542" aria-label="PubMed Central reference 2">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 2" href="http://scholar.google.com/scholar_lookup?&title=Currentstate%20and%20future%20perspectives%20on%20gastroretentive%20drug%20delivery%20systems&journal=Pharmaceutics&doi=10.3390%2Fpharmaceutics11040193&volume=11&publication_year=2019&author=Tripathi%2CJ&author=Thapa%2CP&author=Maharjan%2CR&author=Jeong%2CSH"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="3."><p class="c-article-references__text" id="ref-CR3">New, R. Oral delivery of biologics via the intestine. <i>Pharmaceutics</i> <b>13</b>, 18 (2020).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.3390/pharmaceutics13010018" data-track-item_id="10.3390/pharmaceutics13010018" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.3390%2Fpharmaceutics13010018" aria-label="Article reference 3" data-doi="10.3390/pharmaceutics13010018">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=33374222" aria-label="PubMed reference 3">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824380" aria-label="PubMed Central reference 3">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 3" href="http://scholar.google.com/scholar_lookup?&title=Oral%20delivery%20of%20biologics%20via%20the%20intestine&journal=Pharmaceutics&doi=10.3390%2Fpharmaceutics13010018&volume=13&publication_year=2020&author=New%2CR"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="4."><p class="c-article-references__text" id="ref-CR4">Dahlgren, D. & Lennernas, H. Intestinal permeability and drug absorption: predictive experimental, computational and in vivo approaches. <i>Pharmaceutics</i> <b>11</b>, 411 (2019).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.3390/pharmaceutics11080411" data-track-item_id="10.3390/pharmaceutics11080411" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.3390%2Fpharmaceutics11080411" aria-label="Article reference 4" data-doi="10.3390/pharmaceutics11080411">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BB3cXlvVSgu78%3D" aria-label="CAS reference 4">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=31412551" aria-label="PubMed reference 4">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723276" aria-label="PubMed Central reference 4">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 4" href="http://scholar.google.com/scholar_lookup?&title=Intestinal%20permeability%20and%20drug%20absorption%3A%20predictive%20experimental%2C%20computational%20and%20in%20vivo%20approaches&journal=Pharmaceutics&doi=10.3390%2Fpharmaceutics11080411&volume=11&publication_year=2019&author=Dahlgren%2CD&author=Lennernas%2CH"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="5."><p class="c-article-references__text" id="ref-CR5">Brown, M. T. & Bussell, J. K. Medication adherence: WHO cares? <i>Mayo Clin. Proc.</i> <b>86</b>, 304–314 (2011).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.4065/mcp.2010.0575" data-track-item_id="10.4065/mcp.2010.0575" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.4065%2Fmcp.2010.0575" aria-label="Article reference 5" data-doi="10.4065/mcp.2010.0575">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=21389250" aria-label="PubMed reference 5">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3068890" aria-label="PubMed Central reference 5">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 5" href="http://scholar.google.com/scholar_lookup?&title=Medication%20adherence%3A%20WHO%20cares%3F&journal=Mayo%20Clin.%20Proc.&doi=10.4065%2Fmcp.2010.0575&volume=86&pages=304-314&publication_year=2011&author=Brown%2CMT&author=Bussell%2CJK"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="6."><p class="c-article-references__text" id="ref-CR6">Merril, C. R., Scholl, D. & Adhya, S. L. The prospect for bacteriophage therapy in Western medicine. <i>Nat. Rev. Drug Discov.</i> <b>2</b>, 489–497 (2003).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1038/nrd1111" data-track-item_id="10.1038/nrd1111" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1038%2Fnrd1111" aria-label="Article reference 6" data-doi="10.1038/nrd1111">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD3sXktFOhu7g%3D" aria-label="CAS reference 6">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=12776223" aria-label="PubMed reference 6">PubMed</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 6" href="http://scholar.google.com/scholar_lookup?&title=The%20prospect%20for%20bacteriophage%20therapy%20in%20Western%20medicine&journal=Nat.%20Rev.%20Drug%20Discov.&doi=10.1038%2Fnrd1111&volume=2&pages=489-497&publication_year=2003&author=Merril%2CCR&author=Scholl%2CD&author=Adhya%2CSL"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="7."><p class="c-article-references__text" id="ref-CR7">Barr, J. J. et al. Bacteriophage adhering to mucus provide a non-host-derived immunity. <i>Proc. Natl Acad. Sci. USA</i> <b>110</b>, 10771–10776 (2013).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1073/pnas.1305923110" data-track-item_id="10.1073/pnas.1305923110" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1073%2Fpnas.1305923110" aria-label="Article reference 7" data-doi="10.1073/pnas.1305923110">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC3sXhtFejs7jJ" aria-label="CAS reference 7">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=23690590" aria-label="PubMed reference 7">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3696810" aria-label="PubMed Central reference 7">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 7" href="http://scholar.google.com/scholar_lookup?&title=Bacteriophage%20adhering%20to%20mucus%20provide%20a%20non-host-derived%20immunity&journal=Proc.%20Natl%20Acad.%20Sci.%20USA&doi=10.1073%2Fpnas.1305923110&volume=110&pages=10771-10776&publication_year=2013&author=Barr%2CJJ"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="8."><p class="c-article-references__text" id="ref-CR8">Van Belleghem, J. D., Dabrowska, K., Vaneechoutte, M., Barr, J. J. & Bollyky, P. L. Interactions between bacteriophage, bacteria, and the mammalian immune system. <i>Viruses</i> <b>11</b>, 10 (2018).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.3390/v11010010" data-track-item_id="10.3390/v11010010" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.3390%2Fv11010010" aria-label="Article reference 8" data-doi="10.3390/v11010010">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=30585199" aria-label="PubMed reference 8">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356784" aria-label="PubMed Central reference 8">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 8" href="http://scholar.google.com/scholar_lookup?&title=Interactions%20between%20bacteriophage%2C%20bacteria%2C%20and%20the%20mammalian%20immune%20system&journal=Viruses&doi=10.3390%2Fv11010010&volume=11&publication_year=2018&author=Van%20Belleghem%2CJD&author=Dabrowska%2CK&author=Vaneechoutte%2CM&author=Barr%2CJJ&author=Bollyky%2CPL"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="9."><p class="c-article-references__text" id="ref-CR9">Shkoporov, A. N. et al. The human gut virome is highly diverse, stable, and individual specific. <i>Cell Host Microbe</i> <b>26</b>, 527–541 e525 (2019).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1016/j.chom.2019.09.009" data-track-item_id="10.1016/j.chom.2019.09.009" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1016%2Fj.chom.2019.09.009" aria-label="Article reference 9" data-doi="10.1016/j.chom.2019.09.009">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC1MXhvFCmsbzE" aria-label="CAS reference 9">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=31600503" aria-label="PubMed reference 9">PubMed</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 9" href="http://scholar.google.com/scholar_lookup?&title=The%20human%20gut%20virome%20is%20highly%20diverse%2C%20stable%2C%20and%20individual%20specific&journal=Cell%20Host%20Microbe&doi=10.1016%2Fj.chom.2019.09.009&volume=26&pages=527-541%20e525&publication_year=2019&author=Shkoporov%2CAN"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="10."><p class="c-article-references__text" id="ref-CR10">Minot, S. et al. Rapid evolution of the human gut virome. <i>Proc. Natl Acad. Sci. USA</i> <b>110</b>, 12450–12455 (2013).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1073/pnas.1300833110" data-track-item_id="10.1073/pnas.1300833110" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1073%2Fpnas.1300833110" aria-label="Article reference 10" data-doi="10.1073/pnas.1300833110">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC3sXht1emu7bP" aria-label="CAS reference 10">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=23836644" aria-label="PubMed reference 10">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3725073" aria-label="PubMed Central reference 10">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 10" href="http://scholar.google.com/scholar_lookup?&title=Rapid%20evolution%20of%20the%20human%20gut%20virome&journal=Proc.%20Natl%20Acad.%20Sci.%20USA&doi=10.1073%2Fpnas.1300833110&volume=110&pages=12450-12455&publication_year=2013&author=Minot%2CS"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="11."><p class="c-article-references__text" id="ref-CR11">Shkoporov, A. N. et al. PhiCrAss001 represents the most abundant bacteriophage family in the human gut and infects <i>Bacteroides</i> intestinalis. <i>Nat. Commun.</i> <b>9</b>, 4781 (2018).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1038/s41467-018-07225-7" data-track-item_id="10.1038/s41467-018-07225-7" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1038%2Fs41467-018-07225-7" aria-label="Article reference 11" data-doi="10.1038/s41467-018-07225-7">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=30429469" aria-label="PubMed reference 11">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6235969" aria-label="PubMed Central reference 11">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 11" href="http://scholar.google.com/scholar_lookup?&title=PhiCrAss001%20represents%20the%20most%20abundant%20bacteriophage%20family%20in%20the%20human%20gut%20and%20infects%20Bacteroides%20intestinalis&journal=Nat.%20Commun.&doi=10.1038%2Fs41467-018-07225-7&volume=9&publication_year=2018&author=Shkoporov%2CAN"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="12."><p class="c-article-references__text" id="ref-CR12">Weiss, M. et al. In vivo replication of T4 and T7 bacteriophages in germ-free mice colonized with <i>Escherichia coli</i>. <i>Virology</i> <b>393</b>, 16–23 (2009).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1016/j.virol.2009.07.020" data-track-item_id="10.1016/j.virol.2009.07.020" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1016%2Fj.virol.2009.07.020" aria-label="Article reference 12" data-doi="10.1016/j.virol.2009.07.020">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD1MXhtFyqurfK" aria-label="CAS reference 12">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=19699505" aria-label="PubMed reference 12">PubMed</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 12" href="http://scholar.google.com/scholar_lookup?&title=In%20vivo%20replication%20of%20T4%20and%20T7%20bacteriophages%20in%20germ-free%20mice%20colonized%20with%20Escherichia%20coli&journal=Virology&doi=10.1016%2Fj.virol.2009.07.020&volume=393&pages=16-23&publication_year=2009&author=Weiss%2CM"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="13."><p class="c-article-references__text" id="ref-CR13">Hsu, B. B. et al. Dynamic modulation of the gut microbiota and metabolome by bacteriophages in a mouse model. <i>Cell Host Microbe</i> <b>25</b>, 803–814 (2019).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1016/j.chom.2019.05.001" data-track-item_id="10.1016/j.chom.2019.05.001" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1016%2Fj.chom.2019.05.001" aria-label="Article reference 13" data-doi="10.1016/j.chom.2019.05.001">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BB3cXlsFegtLw%3D" aria-label="CAS reference 13">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=31175044" aria-label="PubMed reference 13">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6579560" aria-label="PubMed Central reference 13">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 13" href="http://scholar.google.com/scholar_lookup?&title=Dynamic%20modulation%20of%20the%20gut%20microbiota%20and%20metabolome%20by%20bacteriophages%20in%20a%20mouse%20model&journal=Cell%20Host%20Microbe&doi=10.1016%2Fj.chom.2019.05.001&volume=25&pages=803-814&publication_year=2019&author=Hsu%2CBB"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="14."><p class="c-article-references__text" id="ref-CR14">Maura, D. et al. Intestinal colonization by enteroaggregative <i>Escherichia coli</i> supports long-term bacteriophage replication in mice. <i>Environ. Microbiol.</i> <b>14</b>, 1844–1854 (2012).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1111/j.1462-2920.2011.02644.x" data-track-item_id="10.1111/j.1462-2920.2011.02644.x" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1111%2Fj.1462-2920.2011.02644.x" aria-label="Article reference 14" data-doi="10.1111/j.1462-2920.2011.02644.x">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC38XhtFOntbrL" aria-label="CAS reference 14">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=22118225" aria-label="PubMed reference 14">PubMed</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 14" href="http://scholar.google.com/scholar_lookup?&title=Intestinal%20colonization%20by%20enteroaggregative%20Escherichia%20coli%20supports%20long-term%20bacteriophage%20replication%20in%20mice&journal=Environ.%20Microbiol.&doi=10.1111%2Fj.1462-2920.2011.02644.x&volume=14&pages=1844-1854&publication_year=2012&author=Maura%2CD"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="15."><p class="c-article-references__text" id="ref-CR15">Javaudin, F., Latour, C., Debarbieux, L. & Lamy-Besnier, Q. Intestinal bacteriophage therapy: looking for optimal efficacy. <i>Clin. Microbiol. Rev.</i> <b>34</b>, e0013621 (2021).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1128/CMR.00136-21" data-track-item_id="10.1128/CMR.00136-21" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1128%2FCMR.00136-21" aria-label="Article reference 15" data-doi="10.1128/CMR.00136-21">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=34668734" aria-label="PubMed reference 15">PubMed</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 15" href="http://scholar.google.com/scholar_lookup?&title=Intestinal%20bacteriophage%20therapy%3A%20looking%20for%20optimal%20efficacy&journal=Clin.%20Microbiol.%20Rev.&doi=10.1128%2FCMR.00136-21&volume=34&publication_year=2021&author=Javaudin%2CF&author=Latour%2CC&author=Debarbieux%2CL&author=Lamy-Besnier%2CQ"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="16."><p class="c-article-references__text" id="ref-CR16">Tennoune, N. et al. Bacterial ClpB heat-shock protein, an antigen-mimetic of the anorexigenic peptide α-MSH, at the origin of eating disorders. <i>Transl. Psychiatry</i> <b>4</b>, e458 (2014).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1038/tp.2014.98" data-track-item_id="10.1038/tp.2014.98" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1038%2Ftp.2014.98" aria-label="Article reference 16" data-doi="10.1038/tp.2014.98">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC2cXhslartLnL" aria-label="CAS reference 16">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=25290265" aria-label="PubMed reference 16">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4350527" aria-label="PubMed Central reference 16">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 16" href="http://scholar.google.com/scholar_lookup?&title=Bacterial%20ClpB%20heat-shock%20protein%2C%20an%20antigen-mimetic%20of%20the%20anorexigenic%20peptide%20%CE%B1-MSH%2C%20at%20the%20origin%20of%20eating%20disorders&journal=Transl.%20Psychiatry&doi=10.1038%2Ftp.2014.98&volume=4&publication_year=2014&author=Tennoune%2CN"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="17."><p class="c-article-references__text" id="ref-CR17">Legrand, R. et al. Commensal <i>Hafnia alvei</i> strain reduces food intake and fat mass in obese mice—a new potential probiotic for appetite and body weight management. <i>Int. J. Obes.</i> <b>44</b>, 1041–1051 (2020).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1038/s41366-019-0515-9" data-track-item_id="10.1038/s41366-019-0515-9" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1038%2Fs41366-019-0515-9" aria-label="Article reference 17" data-doi="10.1038/s41366-019-0515-9">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BB3cXksFGmtA%3D%3D" aria-label="CAS reference 17">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 17" href="http://scholar.google.com/scholar_lookup?&title=Commensal%20Hafnia%20alvei%20strain%20reduces%20food%20intake%20and%20fat%20mass%20in%20obese%20mice%E2%80%94a%20new%20potential%20probiotic%20for%20appetite%20and%20body%20weight%20management&journal=Int.%20J.%20Obes.&doi=10.1038%2Fs41366-019-0515-9&volume=44&pages=1041-1051&publication_year=2020&author=Legrand%2CR"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="18."><p class="c-article-references__text" id="ref-CR18">Miller, E. S. et al. Bacteriophage T4 genome. <i>Microbiol. Mol. Biol. Rev.</i> <b>67</b>, 86–156 (2003).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1128/MMBR.67.1.86-156.2003" data-track-item_id="10.1128/MMBR.67.1.86-156.2003" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1128%2FMMBR.67.1.86-156.2003" aria-label="Article reference 18" data-doi="10.1128/MMBR.67.1.86-156.2003">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD3sXis1yjsLk%3D" aria-label="CAS reference 18">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=12626685" aria-label="PubMed reference 18">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC150520" aria-label="PubMed Central reference 18">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 18" href="http://scholar.google.com/scholar_lookup?&title=Bacteriophage%20T4%20genome&journal=Microbiol.%20Mol.%20Biol.%20Rev.&doi=10.1128%2FMMBR.67.1.86-156.2003&volume=67&pages=86-156&publication_year=2003&author=Miller%2CES"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="19."><p class="c-article-references__text" id="ref-CR19">Luke, K. et al. Microarray analysis of gene expression during bacteriophage T4 infection. <i>Virology</i> <b>299</b>, 182–191 (2002).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1006/viro.2002.1409" data-track-item_id="10.1006/viro.2002.1409" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1006%2Fviro.2002.1409" aria-label="Article reference 19" data-doi="10.1006/viro.2002.1409">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD38Xmt12qsr8%3D" aria-label="CAS reference 19">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=12202221" aria-label="PubMed reference 19">PubMed</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 19" href="http://scholar.google.com/scholar_lookup?&title=Microarray%20analysis%20of%20gene%20expression%20during%20bacteriophage%20T4%20infection&journal=Virology&doi=10.1006%2Fviro.2002.1409&volume=299&pages=182-191&publication_year=2002&author=Luke%2CK"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="20."><p class="c-article-references__text" id="ref-CR20">Grigonyte, A. <i>Engineering Bacteriophages to Enhance their Potential Use in Therapy</i> (University of Warwick, 2018).</p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="21."><p class="c-article-references__text" id="ref-CR21">Duong, M. M., Carmody, C. M. & Nugen, S. R. Phage-based biosensors: in vivo analysis of native T4 phage promoters to enhance reporter enzyme expression. <i>Analyst</i> <b>145</b>, 6291–6297 (2020).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1039/D0AN01413C" data-track-item_id="10.1039/D0AN01413C" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1039%2FD0AN01413C" aria-label="Article reference 21" data-doi="10.1039/D0AN01413C">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BB3cXhsl2ktbrO" aria-label="CAS reference 21">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=32945826" aria-label="PubMed reference 21">PubMed</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 21" href="http://scholar.google.com/scholar_lookup?&title=Phage-based%20biosensors%3A%20in%20vivo%20analysis%20of%20native%20T4%20phage%20promoters%20to%20enhance%20reporter%20enzyme%20expression&journal=Analyst&doi=10.1039%2FD0AN01413C&volume=145&pages=6291-6297&publication_year=2020&author=Duong%2CMM&author=Carmody%2CCM&author=Nugen%2CSR"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="22."><p class="c-article-references__text" id="ref-CR22">Tiemann, B. et al. ModA and ModB, two ADP-ribosyltransferases encoded by bacteriophage T4: catalytic properties and mutation analysis. <i>J. Bacteriol.</i> <b>186</b>, 7262–7272 (2004).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1128/JB.186.21.7262-7272.2004" data-track-item_id="10.1128/JB.186.21.7262-7272.2004" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1128%2FJB.186.21.7262-7272.2004" aria-label="Article reference 22" data-doi="10.1128/JB.186.21.7262-7272.2004">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD2cXptVKntrc%3D" aria-label="CAS reference 22">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=15489438" aria-label="PubMed reference 22">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC523198" aria-label="PubMed Central reference 22">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 22" href="http://scholar.google.com/scholar_lookup?&title=ModA%20and%20ModB%2C%20two%20ADP-ribosyltransferases%20encoded%20by%20bacteriophage%20T4%3A%20catalytic%20properties%20and%20mutation%20analysis&journal=J.%20Bacteriol.&doi=10.1128%2FJB.186.21.7262-7272.2004&volume=186&pages=7262-7272&publication_year=2004&author=Tiemann%2CB"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="23."><p class="c-article-references__text" id="ref-CR23">Fokine, A. et al. Molecular architecture of the prolate head of bacteriophage T4. <i>Proc. Natl Acad. Sci. USA</i> <b>101</b>, 6003–6008 (2004).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1073/pnas.0400444101" data-track-item_id="10.1073/pnas.0400444101" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1073%2Fpnas.0400444101" aria-label="Article reference 23" data-doi="10.1073/pnas.0400444101">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD2cXjsFKnsb4%3D" aria-label="CAS reference 23">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=15071181" aria-label="PubMed reference 23">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC395913" aria-label="PubMed Central reference 23">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 23" href="http://scholar.google.com/scholar_lookup?&title=Molecular%20architecture%20of%20the%20prolate%20head%20of%20bacteriophage%20T4&journal=Proc.%20Natl%20Acad.%20Sci.%20USA&doi=10.1073%2Fpnas.0400444101&volume=101&pages=6003-6008&publication_year=2004&author=Fokine%2CA"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="24."><p class="c-article-references__text" id="ref-CR24">Yap, M. L. & Rossmann, M. G. Structure and function of bacteriophage T4. <i>Future Microbiol.</i> <b>9</b>, 1319–1327 (2014).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.2217/fmb.14.91" data-track-item_id="10.2217/fmb.14.91" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.2217%2Ffmb.14.91" aria-label="Article reference 24" data-doi="10.2217/fmb.14.91">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC2cXitFSiur3J" aria-label="CAS reference 24">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=25517898" aria-label="PubMed reference 24">PubMed</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 24" href="http://scholar.google.com/scholar_lookup?&title=Structure%20and%20function%20of%20bacteriophage%20T4&journal=Future%20Microbiol.&doi=10.2217%2Ffmb.14.91&volume=9&pages=1319-1327&publication_year=2014&author=Yap%2CML&author=Rossmann%2CMG"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="25."><p class="c-article-references__text" id="ref-CR25">Leatham, M. P. et al. Mouse intestine selects nonmotile flhDC mutants of <i>Escherichia coli</i> MG1655 with increased colonizing ability and better utilization of carbon sources. <i>Infect. Immun.</i> <b>73</b>, 8039–8049 (2005).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1128/IAI.73.12.8039-8049.2005" data-track-item_id="10.1128/IAI.73.12.8039-8049.2005" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1128%2FIAI.73.12.8039-8049.2005" aria-label="Article reference 25" data-doi="10.1128/IAI.73.12.8039-8049.2005">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD2MXhtlersbfO" aria-label="CAS reference 25">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=16299298" aria-label="PubMed reference 25">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1307065" aria-label="PubMed Central reference 25">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 25" href="http://scholar.google.com/scholar_lookup?&title=Mouse%20intestine%20selects%20nonmotile%20flhDC%20mutants%20of%20Escherichia%20coli%20MG1655%20with%20increased%20colonizing%20ability%20and%20better%20utilization%20of%20carbon%20sources&journal=Infect.%20Immun.&doi=10.1128%2FIAI.73.12.8039-8049.2005&volume=73&pages=8039-8049&publication_year=2005&author=Leatham%2CMP"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="26."><p class="c-article-references__text" id="ref-CR26">Sweeney, N. J. et al. The <i>Escherichia coli</i> K-12 <i>gntP</i> gene allows <i>E. coli</i> F-18 to occupy a distinct nutritional niche in the streptomycin-treated mouse large intestine. <i>Infect. Immun.</i> <b>64</b>, 3497–3503 (1996).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1128/iai.64.9.3497-3503.1996" data-track-item_id="10.1128/iai.64.9.3497-3503.1996" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1128%2Fiai.64.9.3497-3503.1996" aria-label="Article reference 26" data-doi="10.1128/iai.64.9.3497-3503.1996">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DyaK28XltlKhs7w%3D" aria-label="CAS reference 26">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=8751890" aria-label="PubMed reference 26">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC174254" aria-label="PubMed Central reference 26">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 26" href="http://scholar.google.com/scholar_lookup?&title=The%20Escherichia%20coli%20K-12%20gntP%20gene%20allows%20E.%20coli%20F-18%20to%20occupy%20a%20distinct%20nutritional%20niche%20in%20the%20streptomycin-treated%20mouse%20large%20intestine&journal=Infect.%20Immun.&doi=10.1128%2Fiai.64.9.3497-3503.1996&volume=64&pages=3497-3503&publication_year=1996&author=Sweeney%2CNJ"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="27."><p class="c-article-references__text" id="ref-CR27">Curciarello, R. et al. Human neutrophil elastase proteolytic activity in ulcerative colitis favors the loss of function of therapeutic monoclonal antibodies. <i>J. Inflamm. Res.</i> <b>13</b>, 233–243 (2020).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.2147/JIR.S234710" data-track-item_id="10.2147/JIR.S234710" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.2147%2FJIR.S234710" aria-label="Article reference 27" data-doi="10.2147/JIR.S234710">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BB3cXisFehtLrP" aria-label="CAS reference 27">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=32547155" aria-label="PubMed reference 27">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7251227" aria-label="PubMed Central reference 27">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 27" href="http://scholar.google.com/scholar_lookup?&title=Human%20neutrophil%20elastase%20proteolytic%20activity%20in%20ulcerative%20colitis%20favors%20the%20loss%20of%20function%20of%20therapeutic%20monoclonal%20antibodies&journal=J.%20Inflamm.%20Res.&doi=10.2147%2FJIR.S234710&volume=13&pages=233-243&publication_year=2020&author=Curciarello%2CR"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="28."><p class="c-article-references__text" id="ref-CR28">Barry, R. et al. Faecal neutrophil elastase-antiprotease balance reflects colitis severity. <i>Mucosal Immunol.</i> <b>13</b>, 322–333 (2020).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1038/s41385-019-0235-4" data-track-item_id="10.1038/s41385-019-0235-4" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1038%2Fs41385-019-0235-4" aria-label="Article reference 28" data-doi="10.1038/s41385-019-0235-4">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC1MXit1Kqs7nE" aria-label="CAS reference 28">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=31772324" aria-label="PubMed reference 28">PubMed</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 28" href="http://scholar.google.com/scholar_lookup?&title=Faecal%20neutrophil%20elastase-antiprotease%20balance%20reflects%20colitis%20severity&journal=Mucosal%20Immunol.&doi=10.1038%2Fs41385-019-0235-4&volume=13&pages=322-333&publication_year=2020&author=Barry%2CR"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="29."><p class="c-article-references__text" id="ref-CR29">Herrero-Cervera, A., Soehnlein, O. & Kenne, E. Neutrophils in chronic inflammatory diseases. <i>Cell Mol. Immunol.</i> <b>19</b>, 177–191 (2022).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1038/s41423-021-00832-3" data-track-item_id="10.1038/s41423-021-00832-3" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1038%2Fs41423-021-00832-3" aria-label="Article reference 29" data-doi="10.1038/s41423-021-00832-3">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BB38Xht1Oqur8%3D" aria-label="CAS reference 29">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=35039631" aria-label="PubMed reference 29">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8803838" aria-label="PubMed Central reference 29">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 29" href="http://scholar.google.com/scholar_lookup?&title=Neutrophils%20in%20chronic%20inflammatory%20diseases&journal=Cell%20Mol.%20Immunol.&doi=10.1038%2Fs41423-021-00832-3&volume=19&pages=177-191&publication_year=2022&author=Herrero-Cervera%2CA&author=Soehnlein%2CO&author=Kenne%2CE"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="30."><p class="c-article-references__text" id="ref-CR30">Morohoshi, Y. et al. Inhibition of neutrophil elastase prevents the development of murine dextran sulfate sodium-induced colitis. <i>J. Gastroenterol.</i> <b>41</b>, 318–324 (2006).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="noopener" data-track-label="10.1007/s00535-005-1768-8" data-track-item_id="10.1007/s00535-005-1768-8" data-track-value="article reference" data-track-action="article reference" href="https://link.springer.com/doi/10.1007/s00535-005-1768-8" aria-label="Article reference 30" data-doi="10.1007/s00535-005-1768-8">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD28Xlt1Kqtr8%3D" aria-label="CAS reference 30">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=16741610" aria-label="PubMed reference 30">PubMed</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 30" href="http://scholar.google.com/scholar_lookup?&title=Inhibition%20of%20neutrophil%20elastase%20prevents%20the%20development%20of%20murine%20dextran%20sulfate%20sodium-induced%20colitis&journal=J.%20Gastroenterol.&doi=10.1007%2Fs00535-005-1768-8&volume=41&pages=318-324&publication_year=2006&author=Morohoshi%2CY"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="31."><p class="c-article-references__text" id="ref-CR31">Leborgne, N. G. F., Taddeo, A., Freigang, S. & Benarafa, C. Serpinb1a is dispensable for the development and cytokine response of invariant natural killer T cell subsets. <i>Front. Immunol.</i> <b>11</b>, 562587 (2020).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.3389/fimmu.2020.562587" data-track-item_id="10.3389/fimmu.2020.562587" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.3389%2Ffimmu.2020.562587" aria-label="Article reference 31" data-doi="10.3389/fimmu.2020.562587">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BB3MXitVCrsbc%3D" aria-label="CAS reference 31">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=33262755" aria-label="PubMed reference 31">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686238" aria-label="PubMed Central reference 31">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 31" href="http://scholar.google.com/scholar_lookup?&title=Serpinb1a%20is%20dispensable%20for%20the%20development%20and%20cytokine%20response%20of%20invariant%20natural%20killer%20T%20cell%20subsets&journal=Front.%20Immunol.&doi=10.3389%2Ffimmu.2020.562587&volume=11&publication_year=2020&author=Leborgne%2CNGF&author=Taddeo%2CA&author=Freigang%2CS&author=Benarafa%2CC"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="32."><p class="c-article-references__text" id="ref-CR32">Lin, R. et al. Resolving neutrophils due to TRAM deletion renders protection against experimental sepsis. <i>Inflamm. Res.</i> <b>72</b>, 1733–1744 (2023).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="noopener" data-track-label="10.1007/s00011-023-01779-z" data-track-item_id="10.1007/s00011-023-01779-z" data-track-value="article reference" data-track-action="article reference" href="https://link.springer.com/doi/10.1007/s00011-023-01779-z" aria-label="Article reference 32" data-doi="10.1007/s00011-023-01779-z">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BB3sXhs1OgsrrM" aria-label="CAS reference 32">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=37563334" aria-label="PubMed reference 32">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10727485" aria-label="PubMed Central reference 32">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 32" href="http://scholar.google.com/scholar_lookup?&title=Resolving%20neutrophils%20due%20to%20TRAM%20deletion%20renders%20protection%20against%20experimental%20sepsis&journal=Inflamm.%20Res.&doi=10.1007%2Fs00011-023-01779-z&volume=72&pages=1733-1744&publication_year=2023&author=Lin%2CR"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="33."><p class="c-article-references__text" id="ref-CR33">Zhang, Y. et al. Immune-enhancing neutrophils reprogrammed by subclinical low-dose endotoxin in cancer treatment. <i>EMBO Mol. Med.</i> <b>16</b>, 1886–1900 (2024).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1038/s44321-024-00100-7" data-track-item_id="10.1038/s44321-024-00100-7" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1038%2Fs44321-024-00100-7" aria-label="Article reference 33" data-doi="10.1038/s44321-024-00100-7">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BB2cXis1KqtbnF" aria-label="CAS reference 33">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=39009886" aria-label="PubMed reference 33">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11319772" aria-label="PubMed Central reference 33">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 33" href="http://scholar.google.com/scholar_lookup?&title=Immune-enhancing%20neutrophils%20reprogrammed%20by%20subclinical%20low-dose%20endotoxin%20in%20cancer%20treatment&journal=EMBO%20Mol.%20Med.&doi=10.1038%2Fs44321-024-00100-7&volume=16&pages=1886-1900&publication_year=2024&author=Zhang%2CY"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="34."><p class="c-article-references__text" id="ref-CR34">Chen, G. Y., Tang, J., Zheng, P. & Liu, Y. CD24 and Siglec-10 selectively repress tissue damage-induced immune responses. <i>Science</i> <b>323</b>, 1722–1725 (2009).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1126/science.1168988" data-track-item_id="10.1126/science.1168988" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1126%2Fscience.1168988" aria-label="Article reference 34" data-doi="10.1126/science.1168988">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD1MXjs1Kgtrg%3D" aria-label="CAS reference 34">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=19264983" aria-label="PubMed reference 34">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2765686" aria-label="PubMed Central reference 34">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 34" href="http://scholar.google.com/scholar_lookup?&title=CD24%20and%20Siglec-10%20selectively%20repress%20tissue%20damage-induced%20immune%20responses&journal=Science&doi=10.1126%2Fscience.1168988&volume=323&pages=1722-1725&publication_year=2009&author=Chen%2CGY&author=Tang%2CJ&author=Zheng%2CP&author=Liu%2CY"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="35."><p class="c-article-references__text" id="ref-CR35">Boyapati, R. K., Rossi, A. G., Satsangi, J. & Ho, G. T. Gut mucosal DAMPs in IBD: from mechanisms to therapeutic implications. <i>Mucosal Immunol.</i> <b>9</b>, 567–582 (2016).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1038/mi.2016.14" data-track-item_id="10.1038/mi.2016.14" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1038%2Fmi.2016.14" aria-label="Article reference 35" data-doi="10.1038/mi.2016.14">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC28XjsVKgtro%3D" aria-label="CAS reference 35">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=26931062" aria-label="PubMed reference 35">PubMed</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 35" href="http://scholar.google.com/scholar_lookup?&title=Gut%20mucosal%20DAMPs%20in%20IBD%3A%20from%20mechanisms%20to%20therapeutic%20implications&journal=Mucosal%20Immunol.&doi=10.1038%2Fmi.2016.14&volume=9&pages=567-582&publication_year=2016&author=Boyapati%2CRK&author=Rossi%2CAG&author=Satsangi%2CJ&author=Ho%2CGT"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="36."><p class="c-article-references__text" id="ref-CR36">Geng, S. et al. Monocytes reprogrammed by 4-PBA potently contribute to the resolution of inflammation and atherosclerosis. <i>Circ. Res.</i> <b>135</b>, 856–872 (2024).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1161/CIRCRESAHA.124.325023" data-track-item_id="10.1161/CIRCRESAHA.124.325023" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1161%2FCIRCRESAHA.124.325023" aria-label="Article reference 36" data-doi="10.1161/CIRCRESAHA.124.325023">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BB2cXitVehtL3P" aria-label="CAS reference 36">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=39224974" aria-label="PubMed reference 36">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11424066" aria-label="PubMed Central reference 36">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 36" href="http://scholar.google.com/scholar_lookup?&title=Monocytes%20reprogrammed%20by%204-PBA%20potently%20contribute%20to%20the%20resolution%20of%20inflammation%20and%20atherosclerosis&journal=Circ.%20Res.&doi=10.1161%2FCIRCRESAHA.124.325023&volume=135&pages=856-872&publication_year=2024&author=Geng%2CS"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="37."><p class="c-article-references__text" id="ref-CR37">Wang, X. et al. CD24-Siglec axis is an innate immune checkpoint against metaflammation and metabolic disorder. <i>Cell Metab.</i> <b>34</b>, 1088–1103 (2022).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1016/j.cmet.2022.07.005" data-track-item_id="10.1016/j.cmet.2022.07.005" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1016%2Fj.cmet.2022.07.005" aria-label="Article reference 37" data-doi="10.1016/j.cmet.2022.07.005">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BB38XitV2ksLbO" aria-label="CAS reference 37">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=35921817" aria-label="PubMed reference 37">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9393047" aria-label="PubMed Central reference 37">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 37" href="http://scholar.google.com/scholar_lookup?&title=CD24-Siglec%20axis%20is%20an%20innate%20immune%20checkpoint%20against%20metaflammation%20and%20metabolic%20disorder&journal=Cell%20Metab.&doi=10.1016%2Fj.cmet.2022.07.005&volume=34&pages=1088-1103&publication_year=2022&author=Wang%2CX"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="38."><p class="c-article-references__text" id="ref-CR38">Ahmed, M. A. et al. CD24 is upregulated in inflammatory bowel disease and stimulates cell motility and colony formation. <i>Inflamm. Bowel Dis.</i> <b>16</b>, 795–803 (2010).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1002/ibd.21134" data-track-item_id="10.1002/ibd.21134" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1002%2Fibd.21134" aria-label="Article reference 38" data-doi="10.1002/ibd.21134">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=19998456" aria-label="PubMed reference 38">PubMed</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 38" href="http://scholar.google.com/scholar_lookup?&title=CD24%20is%20upregulated%20in%20inflammatory%20bowel%20disease%20and%20stimulates%20cell%20motility%20and%20colony%20formation&journal=Inflamm.%20Bowel%20Dis.&doi=10.1002%2Fibd.21134&volume=16&pages=795-803&publication_year=2010&author=Ahmed%2CMA"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="39."><p class="c-article-references__text" id="ref-CR39">Dechelotte, P. et al. The probiotic strain <i>H. alvei</i> HA4597((R)) improves weight loss in overweight subjects under moderate hypocaloric diet: a proof-of-concept, multicenter randomized, double-blind placebo-controlled study. <i>Nutrients</i> <b>13</b>, 1902 (2021).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.3390/nu13061902" data-track-item_id="10.3390/nu13061902" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.3390%2Fnu13061902" aria-label="Article reference 39" data-doi="10.3390/nu13061902">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BB3MXhvVeqtbnE" aria-label="CAS reference 39">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=34205871" aria-label="PubMed reference 39">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227740" aria-label="PubMed Central reference 39">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 39" href="http://scholar.google.com/scholar_lookup?&title=The%20probiotic%20strain%20H.%20alvei%20HA4597%28%28R%29%29%20improves%20weight%20loss%20in%20overweight%20subjects%20under%20moderate%20hypocaloric%20diet%3A%20a%20proof-of-concept%2C%20multicenter%20randomized%2C%20double-blind%20placebo-controlled%20study&journal=Nutrients&doi=10.3390%2Fnu13061902&volume=13&publication_year=2021&author=Dechelotte%2CP"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="40."><p class="c-article-references__text" id="ref-CR40">Dominique, M. et al. Effects of bacterial CLPB protein fragments on food intake and PYY secretion. <i>Nutrients</i> <b>13</b>, 2223 (2021).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.3390/nu13072223" data-track-item_id="10.3390/nu13072223" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.3390%2Fnu13072223" aria-label="Article reference 40" data-doi="10.3390/nu13072223">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BB3MXisVWmtLzL" aria-label="CAS reference 40">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=34209507" aria-label="PubMed reference 40">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308458" aria-label="PubMed Central reference 40">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 40" href="http://scholar.google.com/scholar_lookup?&title=Effects%20of%20bacterial%20CLPB%20protein%20fragments%20on%20food%20intake%20and%20PYY%20secretion&journal=Nutrients&doi=10.3390%2Fnu13072223&volume=13&publication_year=2021&author=Dominique%2CM"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="41."><p class="c-article-references__text" id="ref-CR41">Panaro, B. L. et al. The melanocortin-4 receptor is expressed in enteroendocrine L cells and regulates the release of peptide YY and glucagon-like peptide 1 in vivo. <i>Cell Metab.</i> <b>20</b>, 1018–1029 (2014).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1016/j.cmet.2014.10.004" data-track-item_id="10.1016/j.cmet.2014.10.004" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1016%2Fj.cmet.2014.10.004" aria-label="Article reference 41" data-doi="10.1016/j.cmet.2014.10.004">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC2cXitVWrsbrF" aria-label="CAS reference 41">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=25453189" aria-label="PubMed reference 41">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255280" aria-label="PubMed Central reference 41">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 41" href="http://scholar.google.com/scholar_lookup?&title=The%20melanocortin-4%20receptor%20is%20expressed%20in%20enteroendocrine%20L%20cells%20and%20regulates%20the%20release%20of%20peptide%20YY%20and%20glucagon-like%20peptide%201%20in%20vivo&journal=Cell%20Metab.&doi=10.1016%2Fj.cmet.2014.10.004&volume=20&pages=1018-1029&publication_year=2014&author=Panaro%2CBL"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="42."><p class="c-article-references__text" id="ref-CR42">Yeo, G. S. H. et al. The melanocortin pathway and energy homeostasis: from discovery to obesity therapy. <i>Mol. Metab.</i> <b>48</b>, 101206 (2021).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1016/j.molmet.2021.101206" data-track-item_id="10.1016/j.molmet.2021.101206" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1016%2Fj.molmet.2021.101206" aria-label="Article reference 42" data-doi="10.1016/j.molmet.2021.101206">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BB3MXnsVSmu74%3D" aria-label="CAS reference 42">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=33684608" aria-label="PubMed reference 42">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050006" aria-label="PubMed Central reference 42">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 42" href="http://scholar.google.com/scholar_lookup?&title=The%20melanocortin%20pathway%20and%20energy%20homeostasis%3A%20from%20discovery%20to%20obesity%20therapy&journal=Mol.%20Metab.&doi=10.1016%2Fj.molmet.2021.101206&volume=48&publication_year=2021&author=Yeo%2CGSH"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="43."><p class="c-article-references__text" id="ref-CR43">Lourenco, M. et al. The spatial heterogeneity of the gut limits predation and fosters coexistence of bacteria and bacteriophages. <i>Cell Host Microbe</i> <b>28</b>, 390–401 (2020).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1016/j.chom.2020.06.002" data-track-item_id="10.1016/j.chom.2020.06.002" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1016%2Fj.chom.2020.06.002" aria-label="Article reference 43" data-doi="10.1016/j.chom.2020.06.002">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BB3cXhtlegt7bF" aria-label="CAS reference 43">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=32615090" aria-label="PubMed reference 43">PubMed</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 43" href="http://scholar.google.com/scholar_lookup?&title=The%20spatial%20heterogeneity%20of%20the%20gut%20limits%20predation%20and%20fosters%20coexistence%20of%20bacteria%20and%20bacteriophages&journal=Cell%20Host%20Microbe&doi=10.1016%2Fj.chom.2020.06.002&volume=28&pages=390-401&publication_year=2020&author=Lourenco%2CM"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="44."><p class="c-article-references__text" id="ref-CR44">Mangalea, M. R. & Duerkop, B. A. Fitness trade-offs resulting from bacteriophage resistance potentiate synergistic antibacterial strategies. <i>Infect. Immun.</i> <b>88</b>, e00926 (2020).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1128/IAI.00926-19" data-track-item_id="10.1128/IAI.00926-19" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1128%2FIAI.00926-19" aria-label="Article reference 44" data-doi="10.1128/IAI.00926-19">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=32094257" aria-label="PubMed reference 44">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7309606" aria-label="PubMed Central reference 44">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 44" href="http://scholar.google.com/scholar_lookup?&title=Fitness%20trade-offs%20resulting%20from%20bacteriophage%20resistance%20potentiate%20synergistic%20antibacterial%20strategies&journal=Infect.%20Immun.&doi=10.1128%2FIAI.00926-19&volume=88&publication_year=2020&author=Mangalea%2CMR&author=Duerkop%2CBA"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="45."><p class="c-article-references__text" id="ref-CR45">Xu, H. et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. <i>J. Clin. Invest.</i> <b>112</b>, 1821–1830 (2003).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1172/JCI200319451" data-track-item_id="10.1172/JCI200319451" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1172%2FJCI200319451" aria-label="Article reference 45" data-doi="10.1172/JCI200319451">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD3sXhtVSmtLvI" aria-label="CAS reference 45">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=14679177" aria-label="PubMed reference 45">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC296998" aria-label="PubMed Central reference 45">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 45" href="http://scholar.google.com/scholar_lookup?&title=Chronic%20inflammation%20in%20fat%20plays%20a%20crucial%20role%20in%20the%20development%20of%20obesity-related%20insulin%20resistance&journal=J.%20Clin.%20Invest.&doi=10.1172%2FJCI200319451&volume=112&pages=1821-1830&publication_year=2003&author=Xu%2CH"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="46."><p class="c-article-references__text" id="ref-CR46">Hotamisligil, G. S. Inflammation and metabolic disorders. <i>Nature</i> <b>444</b>, 860–867 (2006).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1038/nature05485" data-track-item_id="10.1038/nature05485" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1038%2Fnature05485" aria-label="Article reference 46" data-doi="10.1038/nature05485">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD28XhtlShtrzK" aria-label="CAS reference 46">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=17167474" aria-label="PubMed reference 46">PubMed</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 46" href="http://scholar.google.com/scholar_lookup?&title=Inflammation%20and%20metabolic%20disorders&journal=Nature&doi=10.1038%2Fnature05485&volume=444&pages=860-867&publication_year=2006&author=Hotamisligil%2CGS"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="47."><p class="c-article-references__text" id="ref-CR47">Wellen, K. E. & Hotamisligil, G. S. Inflammation, stress, and diabetes. <i>J. Clin. Invest.</i> <b>115</b>, 1111–1119 (2005).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1172/JCI25102" data-track-item_id="10.1172/JCI25102" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1172%2FJCI25102" aria-label="Article reference 47" data-doi="10.1172/JCI25102">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD2MXktFSksbY%3D" aria-label="CAS reference 47">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=15864338" aria-label="PubMed reference 47">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1087185" aria-label="PubMed Central reference 47">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 47" href="http://scholar.google.com/scholar_lookup?&title=Inflammation%2C%20stress%2C%20and%20diabetes&journal=J.%20Clin.%20Invest.&doi=10.1172%2FJCI25102&volume=115&pages=1111-1119&publication_year=2005&author=Wellen%2CKE&author=Hotamisligil%2CGS"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="48."><p class="c-article-references__text" id="ref-CR48">Tang, C., Chen, S., Qian, H. & Huang, W. Interleukin-23: as a drug target for autoimmune inflammatory diseases. <i>Immunology</i> <b>135</b>, 112–124 (2012).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1111/j.1365-2567.2011.03522.x" data-track-item_id="10.1111/j.1365-2567.2011.03522.x" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1111%2Fj.1365-2567.2011.03522.x" aria-label="Article reference 48" data-doi="10.1111/j.1365-2567.2011.03522.x">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC38Xht1eitLo%3D" aria-label="CAS reference 48">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=22044352" aria-label="PubMed reference 48">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3277713" aria-label="PubMed Central reference 48">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 48" href="http://scholar.google.com/scholar_lookup?&title=Interleukin-23%3A%20as%20a%20drug%20target%20for%20autoimmune%20inflammatory%20diseases&journal=Immunology&doi=10.1111%2Fj.1365-2567.2011.03522.x&volume=135&pages=112-124&publication_year=2012&author=Tang%2CC&author=Chen%2CS&author=Qian%2CH&author=Huang%2CW"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="49."><p class="c-article-references__text" id="ref-CR49">Martins, L. M. S. et al. Interleukin-23 promotes intestinal T helper type17 immunity and ameliorates obesity-associated metabolic syndrome in a murine high-fat diet model. <i>Immunology</i> <b>154</b>, 624–636 (2018).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1111/imm.12946" data-track-item_id="10.1111/imm.12946" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1111%2Fimm.12946" aria-label="Article reference 49" data-doi="10.1111/imm.12946">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC1cXhtFSgurfK" aria-label="CAS reference 49">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=29722014" aria-label="PubMed reference 49">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6050211" aria-label="PubMed Central reference 49">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 49" href="http://scholar.google.com/scholar_lookup?&title=Interleukin-23%20promotes%20intestinal%20T%20helper%20type17%20immunity%20and%20ameliorates%20obesity-associated%20metabolic%20syndrome%20in%20a%20murine%20high-fat%20diet%20model&journal=Immunology&doi=10.1111%2Fimm.12946&volume=154&pages=624-636&publication_year=2018&author=Martins%2CLMS"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="50."><p class="c-article-references__text" id="ref-CR50">Sumarac-Dumanovic, M. et al. Increased activity of interleukin-23/interleukin-17 proinflammatory axis in obese women. <i>Int. J. Obes.</i> <b>33</b>, 151–156 (2009).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1038/ijo.2008.216" data-track-item_id="10.1038/ijo.2008.216" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1038%2Fijo.2008.216" aria-label="Article reference 50" data-doi="10.1038/ijo.2008.216">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD1MXkslyrsA%3D%3D" aria-label="CAS reference 50">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 50" href="http://scholar.google.com/scholar_lookup?&title=Increased%20activity%20of%20interleukin-23%2Finterleukin-17%20proinflammatory%20axis%20in%20obese%20women&journal=Int.%20J.%20Obes.&doi=10.1038%2Fijo.2008.216&volume=33&pages=151-156&publication_year=2009&author=Sumarac-Dumanovic%2CM"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="51."><p class="c-article-references__text" id="ref-CR51">Iwakura, Y. & Ishigame, H. The IL-23/IL-17 axis in inflammation. <i>J. Clin. Invest.</i> <b>116</b>, 1218–1222 (2006).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1172/JCI28508" data-track-item_id="10.1172/JCI28508" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1172%2FJCI28508" aria-label="Article reference 51" data-doi="10.1172/JCI28508">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD28XksVWgu7c%3D" aria-label="CAS reference 51">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=16670765" aria-label="PubMed reference 51">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1451213" aria-label="PubMed Central reference 51">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 51" href="http://scholar.google.com/scholar_lookup?&title=The%20IL-23%2FIL-17%20axis%20in%20inflammation&journal=J.%20Clin.%20Invest.&doi=10.1172%2FJCI28508&volume=116&pages=1218-1222&publication_year=2006&author=Iwakura%2CY&author=Ishigame%2CH"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="52."><p class="c-article-references__text" id="ref-CR52">Kanda, H. et al. MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. <i>J. Clin. Invest.</i> <b>116</b>, 1494–1505 (2006).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1172/JCI26498" data-track-item_id="10.1172/JCI26498" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1172%2FJCI26498" aria-label="Article reference 52" data-doi="10.1172/JCI26498">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD28XlsFWrtLo%3D" aria-label="CAS reference 52">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=16691291" aria-label="PubMed reference 52">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1459069" aria-label="PubMed Central reference 52">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 52" href="http://scholar.google.com/scholar_lookup?&title=MCP-1%20contributes%20to%20macrophage%20infiltration%20into%20adipose%20tissue%2C%20insulin%20resistance%2C%20and%20hepatic%20steatosis%20in%20obesity&journal=J.%20Clin.%20Invest.&doi=10.1172%2FJCI26498&volume=116&pages=1494-1505&publication_year=2006&author=Kanda%2CH"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="53."><p class="c-article-references__text" id="ref-CR53">Panee, J. Monocyte chemoattractant protein 1 (MCP-1) in obesity and diabetes. <i>Cytokine</i> <b>60</b>, 1–12 (2012).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1016/j.cyto.2012.06.018" data-track-item_id="10.1016/j.cyto.2012.06.018" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1016%2Fj.cyto.2012.06.018" aria-label="Article reference 53" data-doi="10.1016/j.cyto.2012.06.018">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC38XpvVOgtLk%3D" aria-label="CAS reference 53">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=22766373" aria-label="PubMed reference 53">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3437929" aria-label="PubMed Central reference 53">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 53" href="http://scholar.google.com/scholar_lookup?&title=Monocyte%20chemoattractant%20protein%201%20%28MCP-1%29%20in%20obesity%20and%20diabetes&journal=Cytokine&doi=10.1016%2Fj.cyto.2012.06.018&volume=60&pages=1-12&publication_year=2012&author=Panee%2CJ"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="54."><p class="c-article-references__text" id="ref-CR54">Sartipy, P. & Loskutoff, D. J. Monocyte chemoattractant protein 1 in obesity and insulin resistance. <i>Proc. Natl Acad. Sci. USA</i> <b>100</b>, 7265–7270 (2003).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1073/pnas.1133870100" data-track-item_id="10.1073/pnas.1133870100" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1073%2Fpnas.1133870100" aria-label="Article reference 54" data-doi="10.1073/pnas.1133870100">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD3sXkslOms70%3D" aria-label="CAS reference 54">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=12756299" aria-label="PubMed reference 54">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC165864" aria-label="PubMed Central reference 54">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 54" href="http://scholar.google.com/scholar_lookup?&title=Monocyte%20chemoattractant%20protein%201%20in%20obesity%20and%20insulin%20resistance&journal=Proc.%20Natl%20Acad.%20Sci.%20USA&doi=10.1073%2Fpnas.1133870100&volume=100&pages=7265-7270&publication_year=2003&author=Sartipy%2CP&author=Loskutoff%2CDJ"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="55."><p class="c-article-references__text" id="ref-CR55">Cani, P. D., Osto, M., Geurts, L. & Everard, A. Involvement of gut microbiota in the development of low-grade inflammation and type 2 diabetes associated with obesity. <i>Gut Microbes</i> <b>3</b>, 279–288 (2012).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.4161/gmic.19625" data-track-item_id="10.4161/gmic.19625" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.4161%2Fgmic.19625" aria-label="Article reference 55" data-doi="10.4161/gmic.19625">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=22572877" aria-label="PubMed reference 55">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3463487" aria-label="PubMed Central reference 55">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 55" href="http://scholar.google.com/scholar_lookup?&title=Involvement%20of%20gut%20microbiota%20in%20the%20development%20of%20low-grade%20inflammation%20and%20type%202%20diabetes%20associated%20with%20obesity&journal=Gut%20Microbes&doi=10.4161%2Fgmic.19625&volume=3&pages=279-288&publication_year=2012&author=Cani%2CPD&author=Osto%2CM&author=Geurts%2CL&author=Everard%2CA"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="56."><p class="c-article-references__text" id="ref-CR56">Tetart, F., Repoila, F., Monod, C. & Krisch, H. M. Bacteriophage T4 host range is expanded by duplications of a small domain of the tail fiber adhesin. <i>J. Mol. Biol.</i> <b>258</b>, 726–731 (1996).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1006/jmbi.1996.0281" data-track-item_id="10.1006/jmbi.1996.0281" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1006%2Fjmbi.1996.0281" aria-label="Article reference 56" data-doi="10.1006/jmbi.1996.0281">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DyaK28XjtFOgtrk%3D" aria-label="CAS reference 56">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=8637004" aria-label="PubMed reference 56">PubMed</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 56" href="http://scholar.google.com/scholar_lookup?&title=Bacteriophage%20T4%20host%20range%20is%20expanded%20by%20duplications%20of%20a%20small%20domain%20of%20the%20tail%20fiber%20adhesin&journal=J.%20Mol.%20Biol.&doi=10.1006%2Fjmbi.1996.0281&volume=258&pages=726-731&publication_year=1996&author=Tetart%2CF&author=Repoila%2CF&author=Monod%2CC&author=Krisch%2CHM"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="57."><p class="c-article-references__text" id="ref-CR57">Zhang, H. et al. Human gut microbiota in obesity and after gastric bypass. <i>Proc. Natl Acad. Sci. USA</i> <b>106</b>, 2365–2370 (2009).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1073/pnas.0812600106" data-track-item_id="10.1073/pnas.0812600106" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1073%2Fpnas.0812600106" aria-label="Article reference 57" data-doi="10.1073/pnas.0812600106">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD1MXit12jtL4%3D" aria-label="CAS reference 57">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=19164560" aria-label="PubMed reference 57">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2629490" aria-label="PubMed Central reference 57">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 57" href="http://scholar.google.com/scholar_lookup?&title=Human%20gut%20microbiota%20in%20obesity%20and%20after%20gastric%20bypass&journal=Proc.%20Natl%20Acad.%20Sci.%20USA&doi=10.1073%2Fpnas.0812600106&volume=106&pages=2365-2370&publication_year=2009&author=Zhang%2CH"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="58."><p class="c-article-references__text" id="ref-CR58">Yun, Y. et al. Comparative analysis of gut microbiota associated with body mass index in a large Korean cohort. <i>BMC Microbiol.</i> <b>17</b>, 151 (2017).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="noopener" data-track-label="10.1186/s12866-017-1052-0" data-track-item_id="10.1186/s12866-017-1052-0" data-track-value="article reference" data-track-action="article reference" href="https://link.springer.com/doi/10.1186/s12866-017-1052-0" aria-label="Article reference 58" data-doi="10.1186/s12866-017-1052-0">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=28676106" aria-label="PubMed reference 58">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5497371" aria-label="PubMed Central reference 58">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 58" href="http://scholar.google.com/scholar_lookup?&title=Comparative%20analysis%20of%20gut%20microbiota%20associated%20with%20body%20mass%20index%20in%20a%20large%20Korean%20cohort&journal=BMC%20Microbiol.&doi=10.1186%2Fs12866-017-1052-0&volume=17&publication_year=2017&author=Yun%2CY"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="59."><p class="c-article-references__text" id="ref-CR59">Edwards, R. A. et al. Global phylogeography and ancient evolution of the widespread human gut virus crAssphage. <i>Nat. Microbiol.</i> <b>4</b>, 1727–1736 (2019).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1038/s41564-019-0494-6" data-track-item_id="10.1038/s41564-019-0494-6" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1038%2Fs41564-019-0494-6" aria-label="Article reference 59" data-doi="10.1038/s41564-019-0494-6">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC1MXhtlChtr%2FP" aria-label="CAS reference 59">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=31285584" aria-label="PubMed reference 59">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7440971" aria-label="PubMed Central reference 59">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 59" href="http://scholar.google.com/scholar_lookup?&title=Global%20phylogeography%20and%20ancient%20evolution%20of%20the%20widespread%20human%20gut%20virus%20crAssphage&journal=Nat.%20Microbiol.&doi=10.1038%2Fs41564-019-0494-6&volume=4&pages=1727-1736&publication_year=2019&author=Edwards%2CRA"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="60."><p class="c-article-references__text" id="ref-CR60">Charbonneau, M. R., Isabella, V. M., Li, N. & Kurtz, C. B. Developing a new class of engineered live bacterial therapeutics to treat human diseases. <i>Nat. Commun.</i> <b>11</b>, 1738 (2020).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1038/s41467-020-15508-1" data-track-item_id="10.1038/s41467-020-15508-1" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1038%2Fs41467-020-15508-1" aria-label="Article reference 60" data-doi="10.1038/s41467-020-15508-1">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BB3cXmvFGltLg%3D" aria-label="CAS reference 60">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=32269218" aria-label="PubMed reference 60">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7142098" aria-label="PubMed Central reference 60">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 60" href="http://scholar.google.com/scholar_lookup?&title=Developing%20a%20new%20class%20of%20engineered%20live%20bacterial%20therapeutics%20to%20treat%20human%20diseases&journal=Nat.%20Commun.&doi=10.1038%2Fs41467-020-15508-1&volume=11&publication_year=2020&author=Charbonneau%2CMR&author=Isabella%2CVM&author=Li%2CN&author=Kurtz%2CCB"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="61."><p class="c-article-references__text" id="ref-CR61">Isabella, V. M. et al. Development of a synthetic live bacterial therapeutic for the human metabolic disease phenylketonuria. <i>Nat. Biotechnol.</i> <b>36</b>, 857–864 (2018).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1038/nbt.4222" data-track-item_id="10.1038/nbt.4222" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1038%2Fnbt.4222" aria-label="Article reference 61" data-doi="10.1038/nbt.4222">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC1cXhsVyltrnE" aria-label="CAS reference 61">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=30102294" aria-label="PubMed reference 61">PubMed</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 61" href="http://scholar.google.com/scholar_lookup?&title=Development%20of%20a%20synthetic%20live%20bacterial%20therapeutic%20for%20the%20human%20metabolic%20disease%20phenylketonuria&journal=Nat.%20Biotechnol.&doi=10.1038%2Fnbt.4222&volume=36&pages=857-864&publication_year=2018&author=Isabella%2CVM"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="62."><p class="c-article-references__text" id="ref-CR62">Kurtz, C. B. et al. An engineered <i>E. coli</i> Nissle improves hyperammonemia and survival in mice and shows dose-dependent exposure in healthy humans. <i>Sci. Transl. Med.</i> <b>11</b>, eaau7975 (2019).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1126/scitranslmed.aau7975" data-track-item_id="10.1126/scitranslmed.aau7975" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1126%2Fscitranslmed.aau7975" aria-label="Article reference 62" data-doi="10.1126/scitranslmed.aau7975">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC1MXhtFektrnJ" aria-label="CAS reference 62">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=30651324" aria-label="PubMed reference 62">PubMed</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 62" href="http://scholar.google.com/scholar_lookup?&title=An%20engineered%20E.%20coli%20Nissle%20improves%20hyperammonemia%20and%20survival%20in%20mice%20and%20shows%20dose-dependent%20exposure%20in%20healthy%20humans&journal=Sci.%20Transl.%20Med.&doi=10.1126%2Fscitranslmed.aau7975&volume=11&publication_year=2019&author=Kurtz%2CCB"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="63."><p class="c-article-references__text" id="ref-CR63">Maura, D., Galtier, M., Le Bouguenec, C. & Debarbieux, L. Virulent bacteriophages can target O104:H4 enteroaggregative <i>Escherichia coli</i> in the mouse intestine. <i>Antimicrob. Agents Chemother.</i> <b>56</b>, 6235–6242 (2012).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1128/AAC.00602-12" data-track-item_id="10.1128/AAC.00602-12" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1128%2FAAC.00602-12" aria-label="Article reference 63" data-doi="10.1128/AAC.00602-12">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC38XhslKlsrbP" aria-label="CAS reference 63">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=23006754" aria-label="PubMed reference 63">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3497199" aria-label="PubMed Central reference 63">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 63" href="http://scholar.google.com/scholar_lookup?&title=Virulent%20bacteriophages%20can%20target%20O104%3AH4%20enteroaggregative%20Escherichia%20coli%20in%20the%20mouse%20intestine&journal=Antimicrob.%20Agents%20Chemother.&doi=10.1128%2FAAC.00602-12&volume=56&pages=6235-6242&publication_year=2012&author=Maura%2CD&author=Galtier%2CM&author=Bouguenec%2CC&author=Debarbieux%2CL"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="64."><p class="c-article-references__text" id="ref-CR64">Geiduschek, E. P. & Kassavetis, G. A. Transcription of the T4 late genes. <i>Virol J.</i> <b>7</b>, 288 (2010).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="noopener" data-track-label="10.1186/1743-422X-7-288" data-track-item_id="10.1186/1743-422X-7-288" data-track-value="article reference" data-track-action="article reference" href="https://link.springer.com/doi/10.1186/1743-422X-7-288" aria-label="Article reference 64" data-doi="10.1186/1743-422X-7-288">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=21029432" aria-label="PubMed reference 64">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2988020" aria-label="PubMed Central reference 64">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 64" href="http://scholar.google.com/scholar_lookup?&title=Transcription%20of%20the%20T4%20late%20genes&journal=Virol%20J.&doi=10.1186%2F1743-422X-7-288&volume=7&publication_year=2010&author=Geiduschek%2CEP&author=Kassavetis%2CGA"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="65."><p class="c-article-references__text" id="ref-CR65">Stirling, F. et al. Rational design of evolutionarily stable microbial kill switches. <i>Mol. Cell</i> <b>68</b>, 686–697 (2017).</p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="66."><p class="c-article-references__text" id="ref-CR66">Rottinghaus, A. G., Ferreiro, A., Fishbein, S. R. S., Dantas, G. & Moon, T. S. Genetically stable CRISPR-based kill switches for engineered microbes. <i>Nat. Commun.</i> <b>13</b>, 672 (2022).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1038/s41467-022-28163-5" data-track-item_id="10.1038/s41467-022-28163-5" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1038%2Fs41467-022-28163-5" aria-label="Article reference 66" data-doi="10.1038/s41467-022-28163-5">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BB38XislKmu74%3D" aria-label="CAS reference 66">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=35115506" aria-label="PubMed reference 66">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8813983" aria-label="PubMed Central reference 66">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 66" href="http://scholar.google.com/scholar_lookup?&title=Genetically%20stable%20CRISPR-based%20kill%20switches%20for%20engineered%20microbes&journal=Nat.%20Commun.&doi=10.1038%2Fs41467-022-28163-5&volume=13&publication_year=2022&author=Rottinghaus%2CAG&author=Ferreiro%2CA&author=Fishbein%2CSRS&author=Dantas%2CG&author=Moon%2CTS"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="67."><p class="c-article-references__text" id="ref-CR67">Smati, M. et al. Quantitative analysis of commensal <i>Escherichia coli</i> populations reveals host-specific enterotypes at the intra-species level. <i>Microbiologyopen</i> <b>4</b>, 604–615 (2015).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1002/mbo3.266" data-track-item_id="10.1002/mbo3.266" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1002%2Fmbo3.266" aria-label="Article reference 67" data-doi="10.1002/mbo3.266">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=26033772" aria-label="PubMed reference 67">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4554456" aria-label="PubMed Central reference 67">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 67" href="http://scholar.google.com/scholar_lookup?&title=Quantitative%20analysis%20of%20commensal%20Escherichia%20coli%20populations%20reveals%20host-specific%20enterotypes%20at%20the%20intra-species%20level&journal=Microbiologyopen&doi=10.1002%2Fmbo3.266&volume=4&pages=604-615&publication_year=2015&author=Smati%2CM"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="68."><p class="c-article-references__text" id="ref-CR68">Tenaillon, O., Skurnik, D., Picard, B. & Denamur, E. The population genetics of commensal <i>Escherichia coli</i>. <i>Nat. Rev. Microbiol.</i> <b>8</b>, 207–217 (2010).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1038/nrmicro2298" data-track-item_id="10.1038/nrmicro2298" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1038%2Fnrmicro2298" aria-label="Article reference 68" data-doi="10.1038/nrmicro2298">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC3cXhvFOjtbY%3D" aria-label="CAS reference 68">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=20157339" aria-label="PubMed reference 68">PubMed</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 68" href="http://scholar.google.com/scholar_lookup?&title=The%20population%20genetics%20of%20commensal%20Escherichia%20coli&journal=Nat.%20Rev.%20Microbiol.&doi=10.1038%2Fnrmicro2298&volume=8&pages=207-217&publication_year=2010&author=Tenaillon%2CO&author=Skurnik%2CD&author=Picard%2CB&author=Denamur%2CE"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="69."><p class="c-article-references__text" id="ref-CR69">Strathdee, S. A., Hatfull, G. F., Mutalik, V. K. & Schooley, R. T. Phage therapy: from biological mechanisms to future directions. <i>Cell</i> <b>186</b>, 17–31 (2023).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1016/j.cell.2022.11.017" data-track-item_id="10.1016/j.cell.2022.11.017" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1016%2Fj.cell.2022.11.017" aria-label="Article reference 69" data-doi="10.1016/j.cell.2022.11.017">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BB3sXltVGjsA%3D%3D" aria-label="CAS reference 69">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=36608652" aria-label="PubMed reference 69">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9827498" aria-label="PubMed Central reference 69">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 69" href="http://scholar.google.com/scholar_lookup?&title=Phage%20therapy%3A%20from%20biological%20mechanisms%20to%20future%20directions&journal=Cell&doi=10.1016%2Fj.cell.2022.11.017&volume=186&pages=17-31&publication_year=2023&author=Strathdee%2CSA&author=Hatfull%2CGF&author=Mutalik%2CVK&author=Schooley%2CRT"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="70."><p class="c-article-references__text" id="ref-CR70">Gogokhia, L. et al. Expansion of bacteriophages is linked to aggravated intestinal inflammation and colitis. <i>Cell Host Microbe</i> <b>25</b>, 285–299 (2019).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1016/j.chom.2019.01.008" data-track-item_id="10.1016/j.chom.2019.01.008" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1016%2Fj.chom.2019.01.008" aria-label="Article reference 70" data-doi="10.1016/j.chom.2019.01.008">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC1MXjtVWnsrY%3D" aria-label="CAS reference 70">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=30763538" aria-label="PubMed reference 70">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885004" aria-label="PubMed Central reference 70">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 70" href="http://scholar.google.com/scholar_lookup?&title=Expansion%20of%20bacteriophages%20is%20linked%20to%20aggravated%20intestinal%20inflammation%20and%20colitis&journal=Cell%20Host%20Microbe&doi=10.1016%2Fj.chom.2019.01.008&volume=25&pages=285-299&publication_year=2019&author=Gogokhia%2CL"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="71."><p class="c-article-references__text" id="ref-CR71">Nguyen, S. et al. Bacteriophage transcytosis provides a mechanism to cross epithelial cell layers. <i>mBio</i> <b>8</b>, e01874 (2017).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1128/mBio.01874-17" data-track-item_id="10.1128/mBio.01874-17" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1128%2FmBio.01874-17" aria-label="Article reference 71" data-doi="10.1128/mBio.01874-17">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC1cXisVKmtbrI" aria-label="CAS reference 71">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=29162715" aria-label="PubMed reference 71">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5698557" aria-label="PubMed Central reference 71">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 71" href="http://scholar.google.com/scholar_lookup?&title=Bacteriophage%20transcytosis%20provides%20a%20mechanism%20to%20cross%20epithelial%20cell%20layers&journal=mBio&doi=10.1128%2FmBio.01874-17&volume=8&publication_year=2017&author=Nguyen%2CS"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="72."><p class="c-article-references__text" id="ref-CR72">Clooney, A. G. et al. Whole-virome analysis sheds light on viral dark matter in inflammatory bowel disease. <i>Cell Host Microbe</i> <b>26</b>, 764–778 (2019).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1016/j.chom.2019.10.009" data-track-item_id="10.1016/j.chom.2019.10.009" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1016%2Fj.chom.2019.10.009" aria-label="Article reference 72" data-doi="10.1016/j.chom.2019.10.009">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC1MXit1amsLzP" aria-label="CAS reference 72">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=31757768" aria-label="PubMed reference 72">PubMed</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 72" href="http://scholar.google.com/scholar_lookup?&title=Whole-virome%20analysis%20sheds%20light%20on%20viral%20dark%20matter%20in%20inflammatory%20bowel%20disease&journal=Cell%20Host%20Microbe&doi=10.1016%2Fj.chom.2019.10.009&volume=26&pages=764-778&publication_year=2019&author=Clooney%2CAG"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="73."><p class="c-article-references__text" id="ref-CR73">Engler, C., Kandzia, R. & Marillonnet, S. A one pot, one step, precision cloning method with high throughput capability. <i>PLoS ONE</i> <b>3</b>, e3647 (2008).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1371/journal.pone.0003647" data-track-item_id="10.1371/journal.pone.0003647" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1371%2Fjournal.pone.0003647" aria-label="Article reference 73" data-doi="10.1371/journal.pone.0003647">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=18985154" aria-label="PubMed reference 73">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2574415" aria-label="PubMed Central reference 73">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 73" href="http://scholar.google.com/scholar_lookup?&title=A%20one%20pot%2C%20one%20step%2C%20precision%20cloning%20method%20with%20high%20throughput%20capability&journal=PLoS%20ONE&doi=10.1371%2Fjournal.pone.0003647&volume=3&publication_year=2008&author=Engler%2CC&author=Kandzia%2CR&author=Marillonnet%2CS"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="74."><p class="c-article-references__text" id="ref-CR74">Yan, Q. & Fong, S. S. Study of in vitro transcriptional binding effects and noise using constitutive promoters combined with UP element sequences in <i>Escherichia coli</i>. <i>J. Biol. Eng.</i> <b>11</b>, 33 (2017).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="noopener" data-track-label="10.1186/s13036-017-0075-2" data-track-item_id="10.1186/s13036-017-0075-2" data-track-value="article reference" data-track-action="article reference" href="https://link.springer.com/doi/10.1186/s13036-017-0075-2" aria-label="Article reference 74" data-doi="10.1186/s13036-017-0075-2">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=29118850" aria-label="PubMed reference 74">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5664571" aria-label="PubMed Central reference 74">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 74" href="http://scholar.google.com/scholar_lookup?&title=Study%20of%20in%20vitro%20transcriptional%20binding%20effects%20and%20noise%20using%20constitutive%20promoters%20combined%20with%20UP%20element%20sequences%20in%20Escherichia%20coli&journal=J.%20Biol.%20Eng.&doi=10.1186%2Fs13036-017-0075-2&volume=11&publication_year=2017&author=Yan%2CQ&author=Fong%2CSS"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="75."><p class="c-article-references__text" id="ref-CR75">Qi, L. S. et al. Repurposing CRISPR as an RNA-guided platform for sequence-specific control of gene expression. <i>Cell</i> <b>152</b>, 1173–1183 (2013).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1016/j.cell.2013.02.022" data-track-item_id="10.1016/j.cell.2013.02.022" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1016%2Fj.cell.2013.02.022" aria-label="Article reference 75" data-doi="10.1016/j.cell.2013.02.022">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC3sXjsFChs7s%3D" aria-label="CAS reference 75">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=23452860" aria-label="PubMed reference 75">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664290" aria-label="PubMed Central reference 75">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 75" href="http://scholar.google.com/scholar_lookup?&title=Repurposing%20CRISPR%20as%20an%20RNA-guided%20platform%20for%20sequence-specific%20control%20of%20gene%20expression&journal=Cell&doi=10.1016%2Fj.cell.2013.02.022&volume=152&pages=1173-1183&publication_year=2013&author=Qi%2CLS"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="76."><p class="c-article-references__text" id="ref-CR76">Silver, S. Acriflavine resistance: a bacteriophage mutation affecting the uptake of dye by the infected bacterial cells. <i>Proc. Natl Acad. Sci. USA</i> <b>53</b>, 24–30 (1965).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1073/pnas.53.1.24" data-track-item_id="10.1073/pnas.53.1.24" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1073%2Fpnas.53.1.24" aria-label="Article reference 76" data-doi="10.1073/pnas.53.1.24">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DyaF2MXmvVaqsA%3D%3D" aria-label="CAS reference 76">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=14283203" aria-label="PubMed reference 76">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC219428" aria-label="PubMed Central reference 76">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 76" href="http://scholar.google.com/scholar_lookup?&title=Acriflavine%20resistance%3A%20a%20bacteriophage%20mutation%20affecting%20the%20uptake%20of%20dye%20by%20the%20infected%20bacterial%20cells&journal=Proc.%20Natl%20Acad.%20Sci.%20USA&doi=10.1073%2Fpnas.53.1.24&volume=53&pages=24-30&publication_year=1965&author=Silver%2CS"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="77."><p class="c-article-references__text" id="ref-CR77">Wang, F. J. & Ripley, L. S. The spectrum of acridine resistant mutants of bacteriophage T4 reveals cryptic effects of the tsL141 DNA polymerase allele on spontaneous mutagenesis. <i>Genetics</i> <b>148</b>, 1655–1665 (1998).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1093/genetics/148.4.1655" data-track-item_id="10.1093/genetics/148.4.1655" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1093%2Fgenetics%2F148.4.1655" aria-label="Article reference 77" data-doi="10.1093/genetics/148.4.1655">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DyaK1cXks1eiurs%3D" aria-label="CAS reference 77">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=9560385" aria-label="PubMed reference 77">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1460093" aria-label="PubMed Central reference 77">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 77" href="http://scholar.google.com/scholar_lookup?&title=The%20spectrum%20of%20acridine%20resistant%20mutants%20of%20bacteriophage%20T4%20reveals%20cryptic%20effects%20of%20the%20tsL141%20DNA%20polymerase%20allele%20on%20spontaneous%20mutagenesis&journal=Genetics&doi=10.1093%2Fgenetics%2F148.4.1655&volume=148&pages=1655-1665&publication_year=1998&author=Wang%2CFJ&author=Ripley%2CLS"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="78."><p class="c-article-references__text" id="ref-CR78">Park, S., Reyer, M. A., McLean, E. L., Liu, W. & Fei, J. An improved method for bacterial immunofluorescence staining to eliminate antibody exclusion from the fixed nucleoid. <i>Biochemistry</i> <b>58</b>, 4457–4465 (2019).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1021/acs.biochem.9b00724" data-track-item_id="10.1021/acs.biochem.9b00724" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1021%2Facs.biochem.9b00724" aria-label="Article reference 78" data-doi="10.1021/acs.biochem.9b00724">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC1MXitVaru7fN" aria-label="CAS reference 78">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=31657208" aria-label="PubMed reference 78">PubMed</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 78" href="http://scholar.google.com/scholar_lookup?&title=An%20improved%20method%20for%20bacterial%20immunofluorescence%20staining%20to%20eliminate%20antibody%20exclusion%20from%20the%20fixed%20nucleoid&journal=Biochemistry&doi=10.1021%2Facs.biochem.9b00724&volume=58&pages=4457-4465&publication_year=2019&author=Park%2CS&author=Reyer%2CMA&author=McLean%2CEL&author=Liu%2CW&author=Fei%2CJ"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="79."><p class="c-article-references__text" id="ref-CR79">De Paepe, M. & Taddei, F. Viruses’ life history: towards a mechanistic basis of a trade-off between survival and reproduction among phages. <i>PLoS Biol.</i> <b>4</b>, e193 (2006).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1371/journal.pbio.0040193" data-track-item_id="10.1371/journal.pbio.0040193" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1371%2Fjournal.pbio.0040193" aria-label="Article reference 79" data-doi="10.1371/journal.pbio.0040193">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=16756387" aria-label="PubMed reference 79">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1475768" aria-label="PubMed Central reference 79">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 79" href="http://scholar.google.com/scholar_lookup?&title=Viruses%E2%80%99%20life%20history%3A%20towards%20a%20mechanistic%20basis%20of%20a%20trade-off%20between%20survival%20and%20reproduction%20among%20phages&journal=PLoS%20Biol.&doi=10.1371%2Fjournal.pbio.0040193&volume=4&publication_year=2006&author=Paepe%2CM&author=Taddei%2CF"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="80."><p class="c-article-references__text" id="ref-CR80">Weichhart, T. <i>mTor: Methods and Protocols</i> (Humana Press, 2012).</p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="81."><p class="c-article-references__text" id="ref-CR81">Charles River Research Model. C57BL/6 Mouse Clinical Pathology Data, C57BL/6 mouse hematology: North American colonies. (2012).</p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="82."><p class="c-article-references__text" id="ref-CR82">Bolyen, E. et al. Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2. <i>Nat. Biotechnol.</i> <b>37</b>, 852–857 (2019).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1038/s41587-019-0209-9" data-track-item_id="10.1038/s41587-019-0209-9" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1038%2Fs41587-019-0209-9" aria-label="Article reference 82" data-doi="10.1038/s41587-019-0209-9">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC1MXhsVeksr%2FO" aria-label="CAS reference 82">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=31341288" aria-label="PubMed reference 82">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7015180" aria-label="PubMed Central reference 82">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 82" href="http://scholar.google.com/scholar_lookup?&title=Reproducible%2C%20interactive%2C%20scalable%20and%20extensible%20microbiome%20data%20science%20using%20QIIME%202&journal=Nat.%20Biotechnol.&doi=10.1038%2Fs41587-019-0209-9&volume=37&pages=852-857&publication_year=2019&author=Bolyen%2CE"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="83."><p class="c-article-references__text" id="ref-CR83">Callahan, B. J. et al. DADA2: high-resolution sample inference from Illumina amplicon data. <i>Nat. Methods</i> <b>13</b>, 581–583 (2016).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1038/nmeth.3869" data-track-item_id="10.1038/nmeth.3869" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1038%2Fnmeth.3869" aria-label="Article reference 83" data-doi="10.1038/nmeth.3869">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC28XosVWitb4%3D" aria-label="CAS reference 83">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=27214047" aria-label="PubMed reference 83">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4927377" aria-label="PubMed Central reference 83">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 83" href="http://scholar.google.com/scholar_lookup?&title=DADA2%3A%20high-resolution%20sample%20inference%20from%20Illumina%20amplicon%20data&journal=Nat.%20Methods&doi=10.1038%2Fnmeth.3869&volume=13&pages=581-583&publication_year=2016&author=Callahan%2CBJ"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="84."><p class="c-article-references__text" id="ref-CR84">Hasegawa, Y., Mark Welch, J. L., Rossetti, B. J. & Borisy, G. G. Preservation of three-dimensional spatial structure in the gut microbiome. <i>PLoS ONE</i> <b>12</b>, e0188257 (2017).</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1371/journal.pone.0188257" data-track-item_id="10.1371/journal.pone.0188257" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1371%2Fjournal.pone.0188257" aria-label="Article reference 84" data-doi="10.1371/journal.pone.0188257">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=29176788" aria-label="PubMed reference 84">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5703541" aria-label="PubMed Central reference 84">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 84" href="http://scholar.google.com/scholar_lookup?&title=Preservation%20of%20three-dimensional%20spatial%20structure%20in%20the%20gut%20microbiome&journal=PLoS%20ONE&doi=10.1371%2Fjournal.pone.0188257&volume=12&publication_year=2017&author=Hasegawa%2CY&author=Mark%20Welch%2CJL&author=Rossetti%2CBJ&author=Borisy%2CGG"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="85."><p class="c-article-references__text" id="ref-CR85">Baker, Z. 16S Illumina sequencing reads. <i>Mendeley Data</i> <a href="https://data.mendeley.com/datasets/pt9m6b9s4z/1" data-track="click_references" data-track-action="external reference" data-track-value="external reference" data-track-label="https://data.mendeley.com/datasets/pt9m6b9s4z/1">data.mendeley.com/datasets/pt9m6b9s4z/1</a> (2024).</p></li></ol><p class="c-article-references__download u-hide-print"><a data-track="click" data-track-action="download citation references" data-track-label="link" rel="nofollow" href="https://citation-needed.springer.com/v2/references/10.1038/s41587-025-02570-7?format=refman&flavour=references">Download references<svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-download-medium"></use></svg></a></p></div></div></div></section></div><section data-title="Acknowledgements"><div class="c-article-section" id="Ack1-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Ack1">Acknowledgements</h2><div class="c-article-section__content" id="Ack1-content"><p>We thank T. Thorn, S. DiLorenzo and J. Cartwright at Virginia Tech for technical assistance, as well as E. Ng at the FLSI Light Microscopy Facility at Virginia Tech for fluorescence microscopy support. Research reported in this publication was supported in part by the National Institutes of Health (R35 GM147484 (to B.B.H.) and R01 AI172133 (to L.L.)) and Virginia Tech Dean’s Discovery Fund (fund 446728 to B.B.H. and. L.L.).</p></div></div></section><section aria-labelledby="author-information" data-title="Author information"><div class="c-article-section" id="author-information-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="author-information">Author information</h2><div class="c-article-section__content" id="author-information-content"><h3 class="c-article__sub-heading" id="affiliations">Authors and Affiliations</h3><ol class="c-article-author-affiliation__list"><li id="Aff1"><p class="c-article-author-affiliation__address">Department of Biological Sciences, Virginia Tech, Blacksburg, VA, USA</p><p class="c-article-author-affiliation__authors-list">Zachary R. Baker, Yao Zhang, Hollyn C. Franklin, Liwu Li & Bryan B. Hsu</p></li><li id="Aff2"><p class="c-article-author-affiliation__address">Fralin Life Sciences Institute, Virginia Tech, Blacksburg, VA, USA</p><p class="c-article-author-affiliation__authors-list">Zachary R. Baker, Hollyn C. Franklin & Bryan B. Hsu</p></li><li id="Aff3"><p class="c-article-author-affiliation__address">Center for Emerging, Zoonotic, and Arthropod-Borne Pathogens, Virginia Tech, Blacksburg, VA, USA</p><p class="c-article-author-affiliation__authors-list">Zachary R. Baker, Hollyn C. Franklin & Bryan B. Hsu</p></li><li id="Aff4"><p class="c-article-author-affiliation__address">Metabolism Core, Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA, USA</p><p class="c-article-author-affiliation__authors-list">Haiyan Zhang</p></li><li id="Aff5"><p class="c-article-author-affiliation__address">Department of Biomedical Sciences and Pathobiology, VA–MD College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA</p><p class="c-article-author-affiliation__authors-list">Priscila B. S. Serpa, Teresa Southard & Bryan B. Hsu</p></li></ol><div class="u-js-hide u-hide-print" data-test="author-info"><span class="c-article__sub-heading">Authors</span><ol class="c-article-authors-search u-list-reset"><li id="auth-Zachary_R_-Baker-Aff1-Aff2-Aff3"><span class="c-article-authors-search__title u-h3 js-search-name">Zachary R. Baker</span><div class="c-article-authors-search__list"><div class="c-article-authors-search__item c-article-authors-search__list-item--left"><a href="/search?author=Zachary%20R.%20Baker" class="c-article-button" data-track="click" data-track-action="author link - publication" data-track-label="link" rel="nofollow">View author publications</a></div><div class="c-article-authors-search__item c-article-authors-search__list-item--right"><p class="search-in-title-js c-article-authors-search__text">You can also search for this author in <span class="c-article-identifiers"><a class="c-article-identifiers__item" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Zachary%20R.%20Baker" data-track="click" data-track-action="author link - pubmed" data-track-label="link" rel="nofollow">PubMed</a><span class="u-hide"> </span><a class="c-article-identifiers__item" href="http://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22Zachary%20R.%20Baker%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en" data-track="click" data-track-action="author link - scholar" data-track-label="link" rel="nofollow">Google Scholar</a></span></p></div></div></li><li id="auth-Yao-Zhang-Aff1"><span class="c-article-authors-search__title u-h3 js-search-name">Yao Zhang</span><div class="c-article-authors-search__list"><div class="c-article-authors-search__item c-article-authors-search__list-item--left"><a href="/search?author=Yao%20Zhang" class="c-article-button" data-track="click" data-track-action="author link - publication" data-track-label="link" rel="nofollow">View author publications</a></div><div class="c-article-authors-search__item c-article-authors-search__list-item--right"><p class="search-in-title-js c-article-authors-search__text">You can also search for this author in <span class="c-article-identifiers"><a class="c-article-identifiers__item" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Yao%20Zhang" data-track="click" data-track-action="author link - pubmed" data-track-label="link" rel="nofollow">PubMed</a><span class="u-hide"> </span><a class="c-article-identifiers__item" href="http://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22Yao%20Zhang%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en" data-track="click" data-track-action="author link - scholar" data-track-label="link" rel="nofollow">Google Scholar</a></span></p></div></div></li><li id="auth-Haiyan-Zhang-Aff4"><span class="c-article-authors-search__title u-h3 js-search-name">Haiyan Zhang</span><div class="c-article-authors-search__list"><div class="c-article-authors-search__item c-article-authors-search__list-item--left"><a href="/search?author=Haiyan%20Zhang" class="c-article-button" data-track="click" data-track-action="author link - publication" data-track-label="link" rel="nofollow">View author publications</a></div><div class="c-article-authors-search__item c-article-authors-search__list-item--right"><p class="search-in-title-js c-article-authors-search__text">You can also search for this author in <span class="c-article-identifiers"><a class="c-article-identifiers__item" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Haiyan%20Zhang" data-track="click" data-track-action="author link - pubmed" data-track-label="link" rel="nofollow">PubMed</a><span class="u-hide"> </span><a class="c-article-identifiers__item" href="http://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22Haiyan%20Zhang%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en" data-track="click" data-track-action="author link - scholar" data-track-label="link" rel="nofollow">Google Scholar</a></span></p></div></div></li><li id="auth-Hollyn_C_-Franklin-Aff1-Aff2-Aff3"><span class="c-article-authors-search__title u-h3 js-search-name">Hollyn C. Franklin</span><div class="c-article-authors-search__list"><div class="c-article-authors-search__item c-article-authors-search__list-item--left"><a href="/search?author=Hollyn%20C.%20Franklin" class="c-article-button" data-track="click" data-track-action="author link - publication" data-track-label="link" rel="nofollow">View author publications</a></div><div class="c-article-authors-search__item c-article-authors-search__list-item--right"><p class="search-in-title-js c-article-authors-search__text">You can also search for this author in <span class="c-article-identifiers"><a class="c-article-identifiers__item" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Hollyn%20C.%20Franklin" data-track="click" data-track-action="author link - pubmed" data-track-label="link" rel="nofollow">PubMed</a><span class="u-hide"> </span><a class="c-article-identifiers__item" href="http://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22Hollyn%20C.%20Franklin%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en" data-track="click" data-track-action="author link - scholar" data-track-label="link" rel="nofollow">Google Scholar</a></span></p></div></div></li><li id="auth-Priscila_B__S_-Serpa-Aff5"><span class="c-article-authors-search__title u-h3 js-search-name">Priscila B. S. Serpa</span><div class="c-article-authors-search__list"><div class="c-article-authors-search__item c-article-authors-search__list-item--left"><a href="/search?author=Priscila%20B.%20S.%20Serpa" class="c-article-button" data-track="click" data-track-action="author link - publication" data-track-label="link" rel="nofollow">View author publications</a></div><div class="c-article-authors-search__item c-article-authors-search__list-item--right"><p class="search-in-title-js c-article-authors-search__text">You can also search for this author in <span class="c-article-identifiers"><a class="c-article-identifiers__item" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Priscila%20B.%20S.%20Serpa" data-track="click" data-track-action="author link - pubmed" data-track-label="link" rel="nofollow">PubMed</a><span class="u-hide"> </span><a class="c-article-identifiers__item" href="http://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22Priscila%20B.%20S.%20Serpa%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en" data-track="click" data-track-action="author link - scholar" data-track-label="link" rel="nofollow">Google Scholar</a></span></p></div></div></li><li id="auth-Teresa-Southard-Aff5"><span class="c-article-authors-search__title u-h3 js-search-name">Teresa Southard</span><div class="c-article-authors-search__list"><div class="c-article-authors-search__item c-article-authors-search__list-item--left"><a href="/search?author=Teresa%20Southard" class="c-article-button" data-track="click" data-track-action="author link - publication" data-track-label="link" rel="nofollow">View author publications</a></div><div class="c-article-authors-search__item c-article-authors-search__list-item--right"><p class="search-in-title-js c-article-authors-search__text">You can also search for this author in <span class="c-article-identifiers"><a class="c-article-identifiers__item" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Teresa%20Southard" data-track="click" data-track-action="author link - pubmed" data-track-label="link" rel="nofollow">PubMed</a><span class="u-hide"> </span><a class="c-article-identifiers__item" href="http://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22Teresa%20Southard%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en" data-track="click" data-track-action="author link - scholar" data-track-label="link" rel="nofollow">Google Scholar</a></span></p></div></div></li><li id="auth-Liwu-Li-Aff1"><span class="c-article-authors-search__title u-h3 js-search-name">Liwu Li</span><div class="c-article-authors-search__list"><div class="c-article-authors-search__item c-article-authors-search__list-item--left"><a href="/search?author=Liwu%20Li" class="c-article-button" data-track="click" data-track-action="author link - publication" data-track-label="link" rel="nofollow">View author publications</a></div><div class="c-article-authors-search__item c-article-authors-search__list-item--right"><p class="search-in-title-js c-article-authors-search__text">You can also search for this author in <span class="c-article-identifiers"><a class="c-article-identifiers__item" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Liwu%20Li" data-track="click" data-track-action="author link - pubmed" data-track-label="link" rel="nofollow">PubMed</a><span class="u-hide"> </span><a class="c-article-identifiers__item" href="http://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22Liwu%20Li%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en" data-track="click" data-track-action="author link - scholar" data-track-label="link" rel="nofollow">Google Scholar</a></span></p></div></div></li><li id="auth-Bryan_B_-Hsu-Aff1-Aff2-Aff3-Aff5"><span class="c-article-authors-search__title u-h3 js-search-name">Bryan B. Hsu</span><div class="c-article-authors-search__list"><div class="c-article-authors-search__item c-article-authors-search__list-item--left"><a href="/search?author=Bryan%20B.%20Hsu" class="c-article-button" data-track="click" data-track-action="author link - publication" data-track-label="link" rel="nofollow">View author publications</a></div><div class="c-article-authors-search__item c-article-authors-search__list-item--right"><p class="search-in-title-js c-article-authors-search__text">You can also search for this author in <span class="c-article-identifiers"><a class="c-article-identifiers__item" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Bryan%20B.%20Hsu" data-track="click" data-track-action="author link - pubmed" data-track-label="link" rel="nofollow">PubMed</a><span class="u-hide"> </span><a class="c-article-identifiers__item" href="http://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22Bryan%20B.%20Hsu%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en" data-track="click" data-track-action="author link - scholar" data-track-label="link" rel="nofollow">Google Scholar</a></span></p></div></div></li></ol></div><h3 class="c-article__sub-heading" id="contributions">Contributions</h3><p>B.B.H. and L.L. conceptualized the project. Z.B. and B.B.H. developed the methodology. Z.B., Y.Z., H.Z., H.F., P.B.S.S. and T.S. conducted the investigation. Z.B. and B.B.H. wrote the original draft of the paper. L.L. and B.B.H. reviewed and edited the paper, provided supervision and secured funding.</p><h3 class="c-article__sub-heading" id="corresponding-author">Corresponding authors</h3><p id="corresponding-author-list">Correspondence to <a id="corresp-c1" href="mailto:lwli@vt.edu">Liwu Li</a> or <a id="corresp-c2" href="mailto:bhsu@vt.edu">Bryan B. Hsu</a>.</p></div></div></section><section data-title="Ethics declarations"><div class="c-article-section" id="ethics-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="ethics">Ethics declarations</h2><div class="c-article-section__content" id="ethics-content"> <h3 class="c-article__sub-heading" id="FPar12">Competing interests</h3> <p>Z.B., L.L. and B.B.H. are inventors on a pending patent application related to the phage-based heterologous gene expression system described in this paper. The other authors declare no competing interests.</p> </div></div></section><section data-title="Peer review"><div class="c-article-section" id="peer-review-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="peer-review">Peer review</h2><div class="c-article-section__content" id="peer-review-content"> <h3 class="c-article__sub-heading" id="FPar11">Peer review information</h3> <p><i>Nature Biotechnology</i> thanks Jeremy Barr, Laurent Debarbieux and Tae Seok Moon for their contribution to the peer review of this work.</p> </div></div></section><section data-title="Additional information"><div class="c-article-section" id="additional-information-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="additional-information">Additional information</h2><div class="c-article-section__content" id="additional-information-content"><p><b>Publisher’s note</b> Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.</p></div></div></section><section data-title="Supplementary information"><div class="c-article-section" id="Sec18-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Sec18">Supplementary information</h2><div class="c-article-section__content" id="Sec18-content"><div data-test="supplementary-info"><div id="figshareContainer" class="c-article-figshare-container" data-test="figshare-container"></div><div class="c-article-supplementary__item" data-test="supp-item" id="MOESM1"><h3 class="c-article-supplementary__title u-h3"><a class="print-link" data-track="click" data-track-action="view supplementary info" data-test="supp-info-link" data-track-label="supplementary information" href="https://static-content.springer.com/esm/art%3A10.1038%2Fs41587-025-02570-7/MediaObjects/41587_2025_2570_MOESM1_ESM.pdf" data-supp-info-image="">Supplementary Information</a></h3><div class="c-article-supplementary__description" data-component="thumbnail-container"><p>Supplementary Figs. 1–7 and Supplementary Tables 1 and 2.</p></div></div><div class="c-article-supplementary__item" data-test="supp-item" id="MOESM2"><h3 class="c-article-supplementary__title u-h3"><a class="print-link" data-track="click" data-track-action="view supplementary info" data-test="supp-info-link" data-track-label="reporting summary" href="https://static-content.springer.com/esm/art%3A10.1038%2Fs41587-025-02570-7/MediaObjects/41587_2025_2570_MOESM2_ESM.pdf" data-supp-info-image="">Reporting Summary</a></h3></div><div class="c-article-supplementary__item" data-test="supp-item" id="MOESM3"><h3 class="c-article-supplementary__title u-h3"><a class="print-link" data-track="click" data-track-action="view supplementary info" data-test="supp-info-link" data-track-label="supplementary data 1" href="https://static-content.springer.com/esm/art%3A10.1038%2Fs41587-025-02570-7/MediaObjects/41587_2025_2570_MOESM3_ESM.xlsx" data-supp-info-image="">Supplementary Data 1</a></h3><div class="c-article-supplementary__description" data-component="thumbnail-container"><p>Supporting data for Supplementary Figs. 1, 3–5 and 7.</p></div></div><div class="c-article-supplementary__item" data-test="supp-item" id="MOESM4"><h3 class="c-article-supplementary__title u-h3"><a class="print-link" data-track="click" data-track-action="view supplementary info" data-test="supp-info-link" data-track-label="supplementary data 2" href="https://static-content.springer.com/esm/art%3A10.1038%2Fs41587-025-02570-7/MediaObjects/41587_2025_2570_MOESM4_ESM.xlsx" data-supp-info-image="">Supplementary Data 2</a></h3><div class="c-article-supplementary__description" data-component="thumbnail-container"><p>Oligonucleotide sequences used in this study.</p></div></div></div></div></div></section><section data-title="Source data"><div class="c-article-section" id="Sec19-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Sec19">Source data</h2><div class="c-article-section__content" id="Sec19-content"><div data-test="supplementary-info"><div class="c-article-supplementary__item" data-test="supp-item" id="MOESM5"><h3 class="c-article-supplementary__title u-h3"><a class="print-link" data-track="click" data-track-action="view supplementary info" data-test="supp-info-link" data-track-label="source data figs. 1–5" href="https://static-content.springer.com/esm/art%3A10.1038%2Fs41587-025-02570-7/MediaObjects/41587_2025_2570_MOESM5_ESM.xlsx" data-supp-info-image="">Source Data Figs. 1–5</a></h3><div class="c-article-supplementary__description" data-component="thumbnail-container"><p>Source data.</p></div></div></div></div></div></section><section data-title="Rights and permissions"><div class="c-article-section" id="rightslink-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="rightslink">Rights and permissions</h2><div class="c-article-section__content" id="rightslink-content"><p>Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</p><p class="c-article-rights"><a data-track="click" data-track-action="view rights and permissions" data-track-label="link" href="https://s100.copyright.com/AppDispatchServlet?title=Sustained%20in%20situ%20protein%20production%20and%20release%20in%20the%20mammalian%20gut%20by%20an%20engineered%20bacteriophage&author=Zachary%20R.%20Baker%20et%20al&contentID=10.1038%2Fs41587-025-02570-7&copyright=The%20Author%28s%29%2C%20under%20exclusive%20licence%20to%20Springer%20Nature%20America%2C%20Inc.&publication=1087-0156&publicationDate=2025-02-18&publisherName=SpringerNature&orderBeanReset=true">Reprints and permissions</a></p></div></div></section><section aria-labelledby="article-info" data-title="About this article"><div class="c-article-section" id="article-info-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="article-info">About this article</h2><div class="c-article-section__content" id="article-info-content"><div class="c-bibliographic-information"><div class="u-hide-print c-bibliographic-information__column c-bibliographic-information__column--border"><a data-crossmark="10.1038/s41587-025-02570-7" target="_blank" rel="noopener" href="https://crossmark.crossref.org/dialog/?doi=10.1038/s41587-025-02570-7" data-track="click" data-track-action="Click Crossmark" data-track-label="link" data-test="crossmark"><img loading="lazy" width="57" height="81" alt="Check for updates. Verify currency and authenticity via CrossMark" src="data:image/svg+xml;base64,<svg height="81" width="57" xmlns="http://www.w3.org/2000/svg"><g fill="none" fill-rule="evenodd"><path d="m17.35 35.45 21.3-14.2v-17.03h-21.3" fill="#989898"/><path d="m38.65 35.45-21.3-14.2v-17.03h21.3" fill="#747474"/><path d="m28 .5c-12.98 0-23.5 10.52-23.5 23.5s10.52 23.5 23.5 23.5 23.5-10.52 23.5-23.5c0-6.23-2.48-12.21-6.88-16.62-4.41-4.4-10.39-6.88-16.62-6.88zm0 41.25c-9.8 0-17.75-7.95-17.75-17.75s7.95-17.75 17.75-17.75 17.75 7.95 17.75 17.75c0 4.71-1.87 9.22-5.2 12.55s-7.84 5.2-12.55 5.2z" fill="#535353"/><path d="m41 36c-5.81 6.23-15.23 7.45-22.43 2.9-7.21-4.55-10.16-13.57-7.03-21.5l-4.92-3.11c-4.95 10.7-1.19 23.42 8.78 29.71 9.97 6.3 23.07 4.22 30.6-4.86z" fill="#9c9c9c"/><path d="m.2 58.45c0-.75.11-1.42.33-2.01s.52-1.09.91-1.5c.38-.41.83-.73 1.34-.94.51-.22 1.06-.32 1.65-.32.56 0 1.06.11 1.51.35.44.23.81.5 1.1.81l-.91 1.01c-.24-.24-.49-.42-.75-.56-.27-.13-.58-.2-.93-.2-.39 0-.73.08-1.05.23-.31.16-.58.37-.81.66-.23.28-.41.63-.53 1.04-.13.41-.19.88-.19 1.39 0 1.04.23 1.86.68 2.46.45.59 1.06.88 1.84.88.41 0 .77-.07 1.07-.23s.59-.39.85-.68l.91 1c-.38.43-.8.76-1.28.99-.47.22-1 .34-1.58.34-.59 0-1.13-.1-1.64-.31-.5-.2-.94-.51-1.31-.91-.38-.4-.67-.9-.88-1.48-.22-.59-.33-1.26-.33-2.02zm8.4-5.33h1.61v2.54l-.05 1.33c.29-.27.61-.51.96-.72s.76-.31 1.24-.31c.73 0 1.27.23 1.61.71.33.47.5 1.14.5 2.02v4.31h-1.61v-4.1c0-.57-.08-.97-.25-1.21-.17-.23-.45-.35-.83-.35-.3 0-.56.08-.79.22-.23.15-.49.36-.78.64v4.8h-1.61zm7.37 6.45c0-.56.09-1.06.26-1.51.18-.45.42-.83.71-1.14.29-.3.63-.54 1.01-.71.39-.17.78-.25 1.18-.25.47 0 .88.08 1.23.24.36.16.65.38.89.67s.42.63.54 1.03c.12.41.18.84.18 1.32 0 .32-.02.57-.07.76h-4.36c.07.62.29 1.1.65 1.44.36.33.82.5 1.38.5.29 0 .57-.04.83-.13s.51-.21.76-.37l.55 1.01c-.33.21-.69.39-1.09.53-.41.14-.83.21-1.26.21-.48 0-.92-.08-1.34-.25-.41-.16-.76-.4-1.07-.7-.31-.31-.55-.69-.72-1.13-.18-.44-.26-.95-.26-1.52zm4.6-.62c0-.55-.11-.98-.34-1.28-.23-.31-.58-.47-1.06-.47-.41 0-.77.15-1.07.45-.31.29-.5.73-.58 1.3zm2.5.62c0-.57.09-1.08.28-1.53.18-.44.43-.82.75-1.13s.69-.54 1.1-.71c.42-.16.85-.24 1.31-.24.45 0 .84.08 1.17.23s.61.34.85.57l-.77 1.02c-.19-.16-.38-.28-.56-.37-.19-.09-.39-.14-.61-.14-.56 0-1.01.21-1.35.63-.35.41-.52.97-.52 1.67 0 .69.17 1.24.51 1.66.34.41.78.62 1.32.62.28 0 .54-.06.78-.17.24-.12.45-.26.64-.42l.67 1.03c-.33.29-.69.51-1.08.65-.39.15-.78.23-1.18.23-.46 0-.9-.08-1.31-.24-.4-.16-.75-.39-1.05-.7s-.53-.69-.7-1.13c-.17-.45-.25-.96-.25-1.53zm6.91-6.45h1.58v6.17h.05l2.54-3.16h1.77l-2.35 2.8 2.59 4.07h-1.75l-1.77-2.98-1.08 1.23v1.75h-1.58zm13.69 1.27c-.25-.11-.5-.17-.75-.17-.58 0-.87.39-.87 1.16v.75h1.34v1.27h-1.34v5.6h-1.61v-5.6h-.92v-1.2l.92-.07v-.72c0-.35.04-.68.13-.98.08-.31.21-.57.4-.79s.42-.39.71-.51c.28-.12.63-.18 1.04-.18.24 0 .48.02.69.07.22.05.41.1.57.17zm.48 5.18c0-.57.09-1.08.27-1.53.17-.44.41-.82.72-1.13.3-.31.65-.54 1.04-.71.39-.16.8-.24 1.23-.24s.84.08 1.24.24c.4.17.74.4 1.04.71s.54.69.72 1.13c.19.45.28.96.28 1.53s-.09 1.08-.28 1.53c-.18.44-.42.82-.72 1.13s-.64.54-1.04.7-.81.24-1.24.24-.84-.08-1.23-.24-.74-.39-1.04-.7c-.31-.31-.55-.69-.72-1.13-.18-.45-.27-.96-.27-1.53zm1.65 0c0 .69.14 1.24.43 1.66.28.41.68.62 1.18.62.51 0 .9-.21 1.19-.62.29-.42.44-.97.44-1.66 0-.7-.15-1.26-.44-1.67-.29-.42-.68-.63-1.19-.63-.5 0-.9.21-1.18.63-.29.41-.43.97-.43 1.67zm6.48-3.44h1.33l.12 1.21h.05c.24-.44.54-.79.88-1.02.35-.24.7-.36 1.07-.36.32 0 .59.05.78.14l-.28 1.4-.33-.09c-.11-.01-.23-.02-.38-.02-.27 0-.56.1-.86.31s-.55.58-.77 1.1v4.2h-1.61zm-47.87 15h1.61v4.1c0 .57.08.97.25 1.2.17.24.44.35.81.35.3 0 .57-.07.8-.22.22-.15.47-.39.73-.73v-4.7h1.61v6.87h-1.32l-.12-1.01h-.04c-.3.36-.63.64-.98.86-.35.21-.76.32-1.24.32-.73 0-1.27-.24-1.61-.71-.33-.47-.5-1.14-.5-2.02zm9.46 7.43v2.16h-1.61v-9.59h1.33l.12.72h.05c.29-.24.61-.45.97-.63.35-.17.72-.26 1.1-.26.43 0 .81.08 1.15.24.33.17.61.4.84.71.24.31.41.68.53 1.11.13.42.19.91.19 1.44 0 .59-.09 1.11-.25 1.57-.16.47-.38.85-.65 1.16-.27.32-.58.56-.94.73-.35.16-.72.25-1.1.25-.3 0-.6-.07-.9-.2s-.59-.31-.87-.56zm0-2.3c.26.22.5.37.73.45.24.09.46.13.66.13.46 0 .84-.2 1.15-.6.31-.39.46-.98.46-1.77 0-.69-.12-1.22-.35-1.61-.23-.38-.61-.57-1.13-.57-.49 0-.99.26-1.52.77zm5.87-1.69c0-.56.08-1.06.25-1.51.16-.45.37-.83.65-1.14.27-.3.58-.54.93-.71s.71-.25 1.08-.25c.39 0 .73.07 1 .2.27.14.54.32.81.55l-.06-1.1v-2.49h1.61v9.88h-1.33l-.11-.74h-.06c-.25.25-.54.46-.88.64-.33.18-.69.27-1.06.27-.87 0-1.56-.32-2.07-.95s-.76-1.51-.76-2.65zm1.67-.01c0 .74.13 1.31.4 1.7.26.38.65.58 1.15.58.51 0 .99-.26 1.44-.77v-3.21c-.24-.21-.48-.36-.7-.45-.23-.08-.46-.12-.7-.12-.45 0-.82.19-1.13.59-.31.39-.46.95-.46 1.68zm6.35 1.59c0-.73.32-1.3.97-1.71.64-.4 1.67-.68 3.08-.84 0-.17-.02-.34-.07-.51-.05-.16-.12-.3-.22-.43s-.22-.22-.38-.3c-.15-.06-.34-.1-.58-.1-.34 0-.68.07-1 .2s-.63.29-.93.47l-.59-1.08c.39-.24.81-.45 1.28-.63.47-.17.99-.26 1.54-.26.86 0 1.51.25 1.93.76s.63 1.25.63 2.21v4.07h-1.32l-.12-.76h-.05c-.3.27-.63.48-.98.66s-.73.27-1.14.27c-.61 0-1.1-.19-1.48-.56-.38-.36-.57-.85-.57-1.46zm1.57-.12c0 .3.09.53.27.67.19.14.42.21.71.21.28 0 .54-.07.77-.2s.48-.31.73-.56v-1.54c-.47.06-.86.13-1.18.23-.31.09-.57.19-.76.31s-.33.25-.41.4c-.09.15-.13.31-.13.48zm6.29-3.63h-.98v-1.2l1.06-.07.2-1.88h1.34v1.88h1.75v1.27h-1.75v3.28c0 .8.32 1.2.97 1.2.12 0 .24-.01.37-.04.12-.03.24-.07.34-.11l.28 1.19c-.19.06-.4.12-.64.17-.23.05-.49.08-.76.08-.4 0-.74-.06-1.02-.18-.27-.13-.49-.3-.67-.52-.17-.21-.3-.48-.37-.78-.08-.3-.12-.64-.12-1.01zm4.36 2.17c0-.56.09-1.06.27-1.51s.41-.83.71-1.14c.29-.3.63-.54 1.01-.71.39-.17.78-.25 1.18-.25.47 0 .88.08 1.23.24.36.16.65.38.89.67s.42.63.54 1.03c.12.41.18.84.18 1.32 0 .32-.02.57-.07.76h-4.37c.08.62.29 1.1.65 1.44.36.33.82.5 1.38.5.3 0 .58-.04.84-.13.25-.09.51-.21.76-.37l.54 1.01c-.32.21-.69.39-1.09.53s-.82.21-1.26.21c-.47 0-.92-.08-1.33-.25-.41-.16-.77-.4-1.08-.7-.3-.31-.54-.69-.72-1.13-.17-.44-.26-.95-.26-1.52zm4.61-.62c0-.55-.11-.98-.34-1.28-.23-.31-.58-.47-1.06-.47-.41 0-.77.15-1.08.45-.31.29-.5.73-.57 1.3zm3.01 2.23c.31.24.61.43.92.57.3.13.63.2.98.2.38 0 .65-.08.83-.23s.27-.35.27-.6c0-.14-.05-.26-.13-.37-.08-.1-.2-.2-.34-.28-.14-.09-.29-.16-.47-.23l-.53-.22c-.23-.09-.46-.18-.69-.3-.23-.11-.44-.24-.62-.4s-.33-.35-.45-.55c-.12-.21-.18-.46-.18-.75 0-.61.23-1.1.68-1.49.44-.38 1.06-.57 1.83-.57.48 0 .91.08 1.29.25s.71.36.99.57l-.74.98c-.24-.17-.49-.32-.73-.42-.25-.11-.51-.16-.78-.16-.35 0-.6.07-.76.21-.17.15-.25.33-.25.54 0 .14.04.26.12.36s.18.18.31.26c.14.07.29.14.46.21l.54.19c.23.09.47.18.7.29s.44.24.64.4c.19.16.34.35.46.58.11.23.17.5.17.82 0 .3-.06.58-.17.83-.12.26-.29.48-.51.68-.23.19-.51.34-.84.45-.34.11-.72.17-1.15.17-.48 0-.95-.09-1.41-.27-.46-.19-.86-.41-1.2-.68z" fill="#535353"/></g></svg>"></a></div><div class="c-bibliographic-information__column"><h3 class="c-article__sub-heading" id="citeas">Cite this article</h3><p class="c-bibliographic-information__citation">Baker, Z.R., Zhang, Y., Zhang, H. <i>et al.</i> Sustained in situ protein production and release in the mammalian gut by an engineered bacteriophage. <i>Nat Biotechnol</i> (2025). https://doi.org/10.1038/s41587-025-02570-7</p><p class="c-bibliographic-information__download-citation u-hide-print"><a data-test="citation-link" data-track="click" data-track-action="download article citation" data-track-label="link" data-track-external="" rel="nofollow" href="https://citation-needed.springer.com/v2/references/10.1038/s41587-025-02570-7?format=refman&flavour=citation">Download citation<svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-download-medium"></use></svg></a></p><ul class="c-bibliographic-information__list" data-test="publication-history"><li class="c-bibliographic-information__list-item"><p>Received<span class="u-hide">: </span><span class="c-bibliographic-information__value"><time datetime="2023-12-14">14 December 2023</time></span></p></li><li class="c-bibliographic-information__list-item"><p>Accepted<span class="u-hide">: </span><span class="c-bibliographic-information__value"><time datetime="2025-01-20">20 January 2025</time></span></p></li><li class="c-bibliographic-information__list-item"><p>Published<span class="u-hide">: </span><span class="c-bibliographic-information__value"><time datetime="2025-02-18">18 February 2025</time></span></p></li><li class="c-bibliographic-information__list-item c-bibliographic-information__list-item--full-width"><p><abbr title="Digital Object Identifier">DOI</abbr><span class="u-hide">: </span><span class="c-bibliographic-information__value">https://doi.org/10.1038/s41587-025-02570-7</span></p></li></ul><div data-component="share-box"><div class="c-article-share-box u-display-none" hidden=""><h3 class="c-article__sub-heading">Share this article</h3><p class="c-article-share-box__description">Anyone you share the following link with will be able to read this content:</p><button class="js-get-share-url c-article-share-box__button" type="button" id="get-share-url" data-track="click" data-track-label="button" data-track-external="" data-track-action="get shareable link">Get shareable link</button><div class="js-no-share-url-container u-display-none" hidden=""><p class="js-c-article-share-box__no-sharelink-info c-article-share-box__no-sharelink-info">Sorry, a shareable link is not currently available for this article.</p></div><div class="js-share-url-container u-display-none" hidden=""><p class="js-share-url c-article-share-box__only-read-input" id="share-url" data-track="click" data-track-label="button" data-track-action="select share url"></p><button class="js-copy-share-url c-article-share-box__button--link-like" type="button" id="copy-share-url" data-track="click" data-track-label="button" data-track-action="copy share url" data-track-external="">Copy to clipboard</button></div><p class="js-c-article-share-box__additional-info c-article-share-box__additional-info"> Provided by the Springer Nature SharedIt content-sharing initiative </p></div></div><div data-component="article-info-list"></div></div></div></div></div></section> </div> </div> </article> </main> <aside class="c-article-extras u-hide-print" aria-label="Article navigation" data-component-reading-companion data-container-type="reading-companion" data-track-component="reading companion"> <div class="js-context-bar-sticky-point-desktop" data-track-context="reading companion"> <noscript> <div class="c-nature-box c-nature-box--side " data-component="entitlement-box"> <div class="js-access-button"> <a href="https://wayf.springernature.com?redirect_uri=https%3A%2F%2Fwww.nature.com%2Farticles%2Fs41587-025-02570-7" class="c-article__button" data-test="ra21"> <svg class="u-icon" width="18" height="18" aria-hidden="true" focusable="false"><use href="#icon-institution"></use></svg> <span class="c-article__button-text">Access through your institution</span> </a> </div> <div class="js-buy-button"> <a href="#access-options" class="c-article__button c-article__button--inverted" data-test="ra21"> <span>Buy or subscribe</span> </a> </div> </div> </noscript> <div class="c-nature-box__wrapper c-nature-box__wrapper--placeholder"> <div class="c-nature-box c-nature-box--side u-display-none u-hide-print" aria-hidden="true" data-component="entitlement-box" id=entitlement-box-right-column > <p class="c-nature-box__text js-text u-display-none" aria-hidden="true"></p> <div class="js-access-button u-display-none"> <a href="https://wayf.springernature.com?redirect_uri=https%3A%2F%2Fwww.nature.com%2Farticles%2Fs41587-025-02570-7" class="c-article__button" aria-hidden="true" data-test="ra21" data-track="click_institution_login" data-track-context="reading companion" data-track-action="institution access" data-track-label="button"> <svg class="u-icon" width="18" height="18" aria-hidden="true" focusable="false"><use xlink:href="#icon-institution"></use></svg> <span class="c-article__button-text">Access through your institution</span> </a> </div> <div class="js-change-institution-button u-display-none"> <a href="https://wayf.springernature.com?redirect_uri=https%3A%2F%2Fwww.nature.com%2Farticles%2Fs41587-025-02570-7" class="c-article__button c-article__button--inverted" aria-hidden="true" data-test="ra21" data-track="click" data-track-action="change institution" data-track-label="button"> <span class="c-article__button-text">Change institution</span> </a> </div> <div class="js-buy-button u-display-none"> <a href="#access-options" class="c-article__button c-article__button--inverted" aria-hidden="true" data-test="ra21" data-track="click" data-track-action="buy or subscribe" data-track-label="button"> <span>Buy or subscribe</span> </a> </div> </div> </div> </div> <div class="c-reading-companion"> <div class="c-reading-companion__sticky" data-component="reading-companion-sticky" data-test="reading-companion-sticky"> <div class="c-reading-companion__panel c-reading-companion__sections c-reading-companion__panel--active" id="tabpanel-sections"> <div class="u-lazy-ad-wrapper u-mt-16 u-hide" data-component-mpu> <div class="c-ad c-ad--300x250"> <div class="c-ad__inner"> <p class="c-ad__label">Advertisement</p> <div id="div-gpt-ad-right-2" class="div-gpt-ad advert medium-rectangle js-ad text-center hide-print grade-c-hide" data-ad-type="right" data-test="right-ad" data-pa11y-ignore data-gpt data-gpt-unitpath="/285/biotech.nature.com/article" data-gpt-sizes="300x250" data-gpt-targeting="type=article;pos=right;artid=s41587-025-02570-7;doi=10.1038/s41587-025-02570-7;subjmeta=1321,2522,326,61,631;kwrd=Applied+microbiology,Bacteriophages,Biotechnology"> <noscript> <a href="//pubads.g.doubleclick.net/gampad/jump?iu=/285/biotech.nature.com/article&sz=300x250&c=524554358&t=pos%3Dright%26type%3Darticle%26artid%3Ds41587-025-02570-7%26doi%3D10.1038/s41587-025-02570-7%26subjmeta%3D1321,2522,326,61,631%26kwrd%3DApplied+microbiology,Bacteriophages,Biotechnology"> <img data-test="gpt-advert-fallback-img" src="//pubads.g.doubleclick.net/gampad/ad?iu=/285/biotech.nature.com/article&sz=300x250&c=524554358&t=pos%3Dright%26type%3Darticle%26artid%3Ds41587-025-02570-7%26doi%3D10.1038/s41587-025-02570-7%26subjmeta%3D1321,2522,326,61,631%26kwrd%3DApplied+microbiology,Bacteriophages,Biotechnology" alt="Advertisement" width="300" height="250"></a> </noscript> </div> </div> </div> </div> </div> <div class="c-reading-companion__panel c-reading-companion__figures c-reading-companion__panel--full-width" id="tabpanel-figures"></div> <div class="c-reading-companion__panel c-reading-companion__references c-reading-companion__panel--full-width" id="tabpanel-references"></div> </div> </div> </aside> </div> <nav class="c-header__dropdown" aria-labelledby="Explore-content" data-test="Explore-content" id="explore" data-track-component="nature-150-split-header"> <div class="c-header__container"> <h2 id="Explore-content" class="c-header__heading c-header__heading--js-hide">Explore content</h2> <ul class="c-header__list c-header__list--js-stack"> <li class="c-header__item"> <a class="c-header__link" href="/nbt/research-articles" data-track="click" data-track-action="research articles" data-track-label="link" data-test="explore-nav-item"> Research articles </a> </li> <li class="c-header__item"> <a class="c-header__link" href="/nbt/reviews-and-analysis" data-track="click" data-track-action="reviews & analysis" data-track-label="link" data-test="explore-nav-item"> Reviews & Analysis </a> </li> <li class="c-header__item"> <a class="c-header__link" href="/nbt/news-and-comment" data-track="click" data-track-action="news & comment" data-track-label="link" data-test="explore-nav-item"> News & Comment </a> </li> <li class="c-header__item"> <a class="c-header__link" href="/nbt/podcasts" data-track="click" data-track-action="podcasts" data-track-label="link" data-test="explore-nav-item"> Podcasts </a> </li> <li class="c-header__item"> <a class="c-header__link" href="/nbt/video" data-track="click" data-track-action="videos" data-track-label="link" data-test="explore-nav-item"> Videos </a> </li> <li class="c-header__item"> <a class="c-header__link" href="/nbt/current-issue" data-track="click" data-track-action="current issue" data-track-label="link" data-test="explore-nav-item"> Current issue </a> </li> <li class="c-header__item"> <a class="c-header__link" href="/nbt/collections" data-track="click" data-track-action="collections" data-track-label="link" data-test="explore-nav-item"> Collections </a> </li> </ul> <ul class="c-header__list c-header__list--js-stack"> <li class="c-header__item"> <a class="c-header__link" href="https://www.facebook.com/NatBiotechnol" data-track="click" data-track-action="facebook" data-track-label="link">Follow us on Facebook </a> </li> <li class="c-header__item"> <a class="c-header__link" href="https://twitter.com/NatureBiotech" data-track="click" data-track-action="twitter" data-track-label="link">Follow us on Twitter </a> </li> <li class="c-header__item c-header__item--hide-lg"> <a data-test="subscribe-button" class="c-header__link" href="https://www.nature.com/nbt/subscribe" data-track="click" data-track-action="subscribe" data-track-label="link"> <span>Subscribe</span> </a> </li> <li class="c-header__item c-header__item--hide-lg"> <a class="c-header__link" href="https://www.nature.com/my-account/alerts/subscribe-journal?list-id=2" rel="nofollow" data-track="click" data-track-action="Sign up for alerts" data-track-external data-track-label="link (mobile dropdown)">Sign up for alerts<svg role="img" aria-hidden="true" focusable="false" height="18" viewBox="0 0 18 18" width="18" xmlns="http://www.w3.org/2000/svg"><path d="m4 10h2.5c.27614237 0 .5.2238576.5.5s-.22385763.5-.5.5h-3.08578644l-1.12132034 1.1213203c-.18753638.1875364-.29289322.4418903-.29289322.7071068v.1715729h14v-.1715729c0-.2652165-.1053568-.5195704-.2928932-.7071068l-1.7071068-1.7071067v-3.4142136c0-2.76142375-2.2385763-5-5-5-2.76142375 0-5 2.23857625-5 5zm3 4c0 1.1045695.8954305 2 2 2s2-.8954305 2-2zm-5 0c-.55228475 0-1-.4477153-1-1v-.1715729c0-.530433.21071368-1.0391408.58578644-1.4142135l1.41421356-1.4142136v-3c0-3.3137085 2.6862915-6 6-6s6 2.6862915 6 6v3l1.4142136 1.4142136c.3750727.3750727.5857864.8837805.5857864 1.4142135v.1715729c0 .5522847-.4477153 1-1 1h-4c0 1.6568542-1.3431458 3-3 3-1.65685425 0-3-1.3431458-3-3z" fill="#fff"/></svg> </a> </li> <li class="c-header__item c-header__item--hide-lg"> <a class="c-header__link" href="https://www.nature.com/nbt.rss" data-track="click" data-track-action="rss feed" data-track-label="link"> <span>RSS feed</span> </a> </li> </ul> </div> </nav> <nav class="c-header__dropdown" aria-labelledby="About-the-journal" id="about-the-journal" data-test="about-the-journal" data-track-component="nature-150-split-header"> <div class="c-header__container"> <h2 id="About-the-journal" class="c-header__heading c-header__heading--js-hide">About the journal</h2> <ul class="c-header__list c-header__list--js-stack"> <li class="c-header__item"> <a class="c-header__link" href="/nbt/aims" data-track="click" data-track-action="aims & scope" data-track-label="link"> Aims & Scope </a> </li> <li class="c-header__item"> <a class="c-header__link" href="/nbt/journal-information" data-track="click" data-track-action="journal information" data-track-label="link"> Journal Information </a> </li> <li class="c-header__item"> <a class="c-header__link" href="/nbt/journal-impact" data-track="click" data-track-action="journal metrics" data-track-label="link"> Journal Metrics </a> </li> <li class="c-header__item"> <a class="c-header__link" href="/nbt/editors" data-track="click" data-track-action="about the editors" data-track-label="link"> About the Editors </a> </li> <li class="c-header__item"> <a class="c-header__link" href="/nbt/research-cross-journal-editorial-team" data-track="click" data-track-action="research cross-journal editorial team" data-track-label="link"> Research Cross-Journal Editorial Team </a> </li> <li class="c-header__item"> <a class="c-header__link" href="/nbt/reviews-cross-journal-editorial-team" data-track="click" data-track-action="reviews cross-journal editorial team" data-track-label="link"> Reviews Cross-Journal Editorial Team </a> </li> <li class="c-header__item"> <a class="c-header__link" href="/nbt/our-publishing-models" data-track="click" data-track-action="our publishing models" data-track-label="link"> Our publishing models </a> </li> <li class="c-header__item"> <a class="c-header__link" href="/nbt/editorial-values-statement" data-track="click" data-track-action="editorial values statement" data-track-label="link"> Editorial Values Statement </a> </li> <li class="c-header__item"> <a class="c-header__link" href="/nbt/editorial-policies" data-track="click" data-track-action="editorial policies" data-track-label="link"> Editorial Policies </a> </li> <li class="c-header__item"> <a class="c-header__link" href="/nbt/content" data-track="click" data-track-action="content types" data-track-label="link"> Content Types </a> </li> <li class="c-header__item"> <a class="c-header__link" href="/nbt/web-feeds" data-track="click" data-track-action="web feeds" data-track-label="link"> Web Feeds </a> </li> <li class="c-header__item"> <a class="c-header__link" href="/nbt/posters" data-track="click" data-track-action="posters" data-track-label="link"> Posters </a> </li> <li class="c-header__item"> <a class="c-header__link" href="/nbt/contact" data-track="click" data-track-action="contact" data-track-label="link"> Contact </a> </li> </ul> </div> </nav> <nav class="c-header__dropdown" aria-labelledby="Publish-with-us-label" id="publish-with-us" data-test="publish-with-us" data-track-component="nature-150-split-header"> <div class="c-header__container"> <h2 id="Publish-with-us-label" class="c-header__heading c-header__heading--js-hide">Publish with us</h2> <ul class="c-header__list c-header__list--js-stack"> <li class="c-header__item"> <a class="c-header__link" href="/nbt/submission-guidelines" data-track="click" data-track-action="submission guidelines" data-track-label="link"> Submission Guidelines </a> </li> <li class="c-header__item"> <a class="c-header__link" href="/nbt/for-reviewers" data-track="click" data-track-action="for reviewers" data-track-label="link"> For Reviewers </a> </li> <li class="c-header__item"> <a class="c-header__link" data-test="nature-author-services" data-track="nav_language_services" data-track-context="header publish with us dropdown menu" data-track-action="manuscript author services" data-track-label="link manuscript author services" href="https://authorservices.springernature.com/go/sn/?utm_source=For+Authors&utm_medium=Website_Nature&utm_campaign=Platform+Experimentation+2022&utm_id=PE2022"> Language editing services </a> </li> <li class="c-header__item c-header__item--keyline"> <a class="c-header__link" href="https://mts-nbt.nature.com/cgi-bin/main.plex" data-track="click_submit_manuscript" data-track-context="submit link in Nature header dropdown menu" data-track-action="submit manuscript" data-track-label="link (publish with us dropdown menu)" data-track-external data-gtm-criteo="submit-manuscript">Submit manuscript<svg role="img" aria-hidden="true" focusable="false" height="18" viewBox="0 0 18 18" width="18" xmlns="http://www.w3.org/2000/svg"><path d="m15 0c1.1045695 0 2 .8954305 2 2v5.5c0 .27614237-.2238576.5-.5.5s-.5-.22385763-.5-.5v-5.5c0-.51283584-.3860402-.93550716-.8833789-.99327227l-.1166211-.00672773h-9v3c0 1.1045695-.8954305 2-2 2h-3v10c0 .5128358.38604019.9355072.88337887.9932723l.11662113.0067277h7.5c.27614237 0 .5.2238576.5.5s-.22385763.5-.5.5h-7.5c-1.1045695 0-2-.8954305-2-2v-10.17157288c0-.53043297.21071368-1.0391408.58578644-1.41421356l3.82842712-3.82842712c.37507276-.37507276.88378059-.58578644 1.41421356-.58578644zm-.5442863 8.18867991 3.3545404 3.35454039c.2508994.2508994.2538696.6596433.0035959.909917-.2429543.2429542-.6561449.2462671-.9065387-.0089489l-2.2609825-2.3045251.0010427 7.2231989c0 .3569916-.2898381.6371378-.6473715.6371378-.3470771 0-.6473715-.2852563-.6473715-.6371378l-.0010428-7.2231995-2.2611222 2.3046654c-.2531661.2580415-.6562868.2592444-.9065605.0089707-.24295423-.2429542-.24865597-.6576651.0036132-.9099343l3.3546673-3.35466731c.2509089-.25090888.6612706-.25227691.9135302-.00001728zm-.9557137-3.18867991c.2761424 0 .5.22385763.5.5s-.2238576.5-.5.5h-6c-.27614237 0-.5-.22385763-.5-.5s.22385763-.5.5-.5zm-8.5-3.587-3.587 3.587h2.587c.55228475 0 1-.44771525 1-1zm8.5 1.587c.2761424 0 .5.22385763.5.5s-.2238576.5-.5.5h-6c-.27614237 0-.5-.22385763-.5-.5s.22385763-.5.5-.5z" fill="#fff"/></svg> </a> </li> </ul> </div> </nav> <div id="search-menu" class="c-header__dropdown c-header__dropdown--full-width" data-track-component="nature-150-split-header"> <div class="c-header__container"> <h2 class="c-header__visually-hidden">Search</h2> <form class="c-header__search-form" action="/search" method="get" role="search" autocomplete="off" data-test="inline-search"> <label class="c-header__heading" for="keywords">Search articles by subject, keyword or author</label> <div class="c-header__search-layout c-header__search-layout--max-width"> <div> <input type="text" required="" class="c-header__input" id="keywords" name="q" value=""> </div> <div class="c-header__search-layout"> <div> <label for="results-from" class="c-header__visually-hidden">Show results from</label> <select id="results-from" name="journal" class="c-header__select"> <option value="" selected>All journals</option> <option value="nbt">This journal</option> </select> </div> <div> <button type="submit" class="c-header__search-button">Search</button> </div> </div> </div> </form> <div class="c-header__flush"> <a class="c-header__link" href="/search/advanced" data-track="click" data-track-action="advanced search" data-track-label="link"> Advanced search </a> </div> <h3 class="c-header__heading c-header__heading--keyline">Quick links</h3> <ul class="c-header__list"> <li><a class="c-header__link" href="/subjects" data-track="click" data-track-action="explore articles by subject" data-track-label="link">Explore articles by subject</a></li> <li><a class="c-header__link" href="/naturecareers" data-track="click" data-track-action="find a job" data-track-label="link">Find a job</a></li> <li><a class="c-header__link" href="/authors/index.html" data-track="click" data-track-action="guide to authors" data-track-label="link">Guide to authors</a></li> <li><a class="c-header__link" href="/authors/editorial_policies/" data-track="click" data-track-action="editorial policies" data-track-label="link">Editorial policies</a></li> </ul> </div> </div> <footer class="composite-layer" itemscope itemtype="http://schema.org/Periodical"> <meta itemprop="publisher" content="Springer Nature"> <div class="u-mt-16 u-mb-16"> <div class="u-container"> <div class="u-display-flex u-flex-wrap u-justify-content-space-between"> <p class="c-meta u-ma-0 u-flex-shrink"> <span class="c-meta__item"> Nature Biotechnology (<i>Nat Biotechnol</i>) </span> <span class="c-meta__item"> <abbr title="International Standard Serial Number">ISSN</abbr> <span itemprop="onlineIssn">1546-1696</span> (online) </span> <span class="c-meta__item"> <abbr title="International Standard Serial Number">ISSN</abbr> <span itemprop="printIssn">1087-0156</span> (print) </span> </p> </div> </div> </div> <div class="c-footer"> <div class="u-hide-print" data-track-component="footer"> <h2 class="u-visually-hidden">nature.com sitemap</h2> <div class="c-footer__container"> <div class="c-footer__grid c-footer__group--separator"> <div class="c-footer__group"> <h3 class="c-footer__heading u-mt-0">About Nature Portfolio</h3> <ul class="c-footer__list"> <li class="c-footer__item"><a class="c-footer__link" href="https://www.nature.com/npg_/company_info/index.html" data-track="click" data-track-action="about us" data-track-label="link">About us</a></li> <li class="c-footer__item"><a class="c-footer__link" href="https://www.nature.com/npg_/press_room/press_releases.html" data-track="click" data-track-action="press releases" data-track-label="link">Press releases</a></li> <li class="c-footer__item"><a class="c-footer__link" href="https://press.nature.com/" data-track="click" data-track-action="press office" data-track-label="link">Press office</a></li> <li class="c-footer__item"><a class="c-footer__link" href="https://support.nature.com/support/home" data-track="click" data-track-action="contact us" data-track-label="link">Contact us</a></li> </ul> </div> <div class="c-footer__group"> <h3 class="c-footer__heading u-mt-0">Discover content</h3> <ul class="c-footer__list"> <li class="c-footer__item"><a class="c-footer__link" href="https://www.nature.com/siteindex" data-track="click" data-track-action="journals a-z" data-track-label="link">Journals A-Z</a></li> <li class="c-footer__item"><a class="c-footer__link" href="https://www.nature.com/subjects" data-track="click" data-track-action="article by subject" data-track-label="link">Articles by subject</a></li> <li class="c-footer__item"><a class="c-footer__link" href="https://www.protocols.io/" data-track="click" data-track-action="protocols.io" data-track-label="link">protocols.io</a></li> <li class="c-footer__item"><a class="c-footer__link" href="https://www.natureindex.com/" data-track="click" data-track-action="nature index" data-track-label="link">Nature Index</a></li> </ul> </div> <div class="c-footer__group"> <h3 class="c-footer__heading u-mt-0">Publishing policies</h3> <ul class="c-footer__list"> <li class="c-footer__item"><a class="c-footer__link" href="https://www.nature.com/authors/editorial_policies" data-track="click" data-track-action="Nature portfolio policies" data-track-label="link">Nature portfolio policies</a></li> <li class="c-footer__item"><a class="c-footer__link" href="https://www.nature.com/nature-research/open-access" data-track="click" data-track-action="open access" data-track-label="link">Open access</a></li> </ul> </div> <div class="c-footer__group"> <h3 class="c-footer__heading u-mt-0">Author & Researcher services</h3> <ul class="c-footer__list"> <li class="c-footer__item"><a class="c-footer__link" href="https://www.nature.com/reprints" data-track="click" data-track-action="reprints and permissions" data-track-label="link">Reprints & permissions</a></li> <li class="c-footer__item"><a class="c-footer__link" href="https://www.springernature.com/gp/authors/research-data" data-track="click" data-track-action="data research service" data-track-label="link">Research data</a></li> <li class="c-footer__item"><a class="c-footer__link" href="https://authorservices.springernature.com/language-editing/" data-track="click" data-track-action="language editing" data-track-label="link">Language editing</a></li> <li class="c-footer__item"><a class="c-footer__link" href="https://authorservices.springernature.com/scientific-editing/" data-track="click" data-track-action="scientific editing" data-track-label="link">Scientific editing</a></li> <li class="c-footer__item"><a class="c-footer__link" href="https://masterclasses.nature.com/" data-track="click" data-track-action="nature masterclasses" data-track-label="link">Nature Masterclasses</a></li> <li class="c-footer__item"><a class="c-footer__link" href="https://solutions.springernature.com/" data-track="click" data-track-action="research solutions" data-track-label="link">Research Solutions</a></li> </ul> </div> <div class="c-footer__group"> <h3 class="c-footer__heading u-mt-0">Libraries & institutions</h3> <ul class="c-footer__list"> <li class="c-footer__item"><a class="c-footer__link" href="https://www.springernature.com/gp/librarians/tools-services" data-track="click" data-track-action="librarian service and tools" data-track-label="link">Librarian service & tools</a></li> <li class="c-footer__item"><a class="c-footer__link" href="https://www.springernature.com/gp/librarians/manage-your-account/librarianportal" data-track="click" data-track-action="librarian portal" data-track-label="link">Librarian portal</a></li> <li class="c-footer__item"><a class="c-footer__link" href="https://www.nature.com/openresearch/about-open-access/information-for-institutions" data-track="click" data-track-action="open research" data-track-label="link">Open research</a></li> <li class="c-footer__item"><a class="c-footer__link" href="https://www.springernature.com/gp/librarians/recommend-to-your-library" data-track="click" data-track-action="Recommend to library" data-track-label="link">Recommend to library</a></li> </ul> </div> <div class="c-footer__group"> <h3 class="c-footer__heading u-mt-0">Advertising & partnerships</h3> <ul class="c-footer__list"> <li class="c-footer__item"><a class="c-footer__link" href="https://partnerships.nature.com/product/digital-advertising/" data-track="click" data-track-action="advertising" data-track-label="link">Advertising</a></li> <li class="c-footer__item"><a class="c-footer__link" href="https://partnerships.nature.com/" data-track="click" data-track-action="partnerships and services" data-track-label="link">Partnerships & Services</a></li> <li class="c-footer__item"><a class="c-footer__link" href="https://partnerships.nature.com/media-kits/" data-track="click" data-track-action="media kits" data-track-label="link">Media kits</a> </li> <li class="c-footer__item"><a class="c-footer__link" href="https://partnerships.nature.com/product/branded-content-native-advertising/" data-track-action="branded content" data-track-label="link">Branded content</a></li> </ul> </div> <div class="c-footer__group"> <h3 class="c-footer__heading u-mt-0">Professional development</h3> <ul class="c-footer__list"> <li class="c-footer__item"><a class="c-footer__link" href="https://www.nature.com/naturecareers/" data-track="click" data-track-action="nature careers" data-track-label="link">Nature Careers</a></li> <li class="c-footer__item"><a class="c-footer__link" href="https://conferences.nature.com" data-track="click" data-track-action="nature conferences" data-track-label="link">Nature<span class="u-visually-hidden"> </span> Conferences</a></li> </ul> </div> <div class="c-footer__group"> <h3 class="c-footer__heading u-mt-0">Regional websites</h3> <ul class="c-footer__list"> <li class="c-footer__item"><a class="c-footer__link" href="https://www.nature.com/natafrica" data-track="click" data-track-action="nature africa" data-track-label="link">Nature Africa</a></li> <li class="c-footer__item"><a class="c-footer__link" href="http://www.naturechina.com" data-track="click" data-track-action="nature china" data-track-label="link">Nature China</a></li> <li class="c-footer__item"><a class="c-footer__link" href="https://www.nature.com/nindia" data-track="click" data-track-action="nature india" data-track-label="link">Nature India</a></li> <li class="c-footer__item"><a class="c-footer__link" href="https://www.nature.com/natitaly" data-track="click" data-track-action="nature Italy" data-track-label="link">Nature Italy</a></li> <li class="c-footer__item"><a class="c-footer__link" href="https://www.natureasia.com/ja-jp" data-track="click" data-track-action="nature japan" data-track-label="link">Nature Japan</a></li> <li class="c-footer__item"><a class="c-footer__link" href="https://www.nature.com/nmiddleeast" data-track="click" data-track-action="nature middle east" data-track-label="link">Nature Middle East</a></li> </ul> </div> </div> </div> <div class="c-footer__container"> <ul class="c-footer__links"> <li class="c-footer__item"><a class="c-footer__link" href="https://www.nature.com/info/privacy" data-track="click" data-track-action="privacy policy" data-track-label="link">Privacy Policy</a></li> <li class="c-footer__item"><a class="c-footer__link" href="https://www.nature.com/info/cookies" data-track="click" data-track-action="use of cookies" data-track-label="link">Use of cookies</a></li> <li class="c-footer__item"> <button class="optanon-toggle-display c-footer__link" onclick="javascript:;" data-cc-action="preferences" data-track="click" data-track-action="manage cookies" data-track-label="link">Your privacy choices/Manage cookies </button> </li> <li class="c-footer__item"><a class="c-footer__link" href="https://www.nature.com/info/legal-notice" data-track="click" data-track-action="legal notice" data-track-label="link">Legal notice</a></li> <li class="c-footer__item"><a class="c-footer__link" href="https://www.nature.com/info/accessibility-statement" data-track="click" data-track-action="accessibility statement" data-track-label="link">Accessibility statement</a></li> <li class="c-footer__item"><a class="c-footer__link" href="https://www.nature.com/info/terms-and-conditions" data-track="click" data-track-action="terms and conditions" data-track-label="link">Terms & Conditions</a></li> <li class="c-footer__item"><a class="c-footer__link" href="https://www.springernature.com/ccpa" data-track="click" data-track-action="california privacy statement" data-track-label="link">Your US state privacy rights</a></li> </ul> </div> </div> <div class="c-footer__container"> <a href="https://www.springernature.com/" class="c-footer__link"> <img src="/static/images/logos/sn-logo-white-ea63208b81.svg" alt="Springer Nature" loading="lazy" width="200" height="20"/> </a> <p class="c-footer__legal" data-test="copyright">© 2025 Springer Nature Limited</p> </div> </div> <div class="u-visually-hidden" aria-hidden="true"> <?xml version="1.0" encoding="UTF-8"?><!DOCTYPE svg PUBLIC "-//W3C//DTD SVG 1.1//EN" "http://www.w3.org/Graphics/SVG/1.1/DTD/svg11.dtd"><svg xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><defs><path id="a" d="M0 .74h56.72v55.24H0z"/></defs><symbol id="icon-access" viewBox="0 0 18 18"><path d="m14 8c.5522847 0 1 .44771525 1 1v7h2.5c.2761424 0 .5.2238576.5.5v1.5h-18v-1.5c0-.2761424.22385763-.5.5-.5h2.5v-7c0-.55228475.44771525-1 1-1s1 .44771525 1 1v6.9996556h8v-6.9996556c0-.55228475.4477153-1 1-1zm-8 0 2 1v5l-2 1zm6 0v7l-2-1v-5zm-2.42653766-7.59857636 7.03554716 4.92488299c.4162533.29137735.5174853.86502537.226108 1.28127873-.1721584.24594054-.4534847.39241464-.7536934.39241464h-14.16284822c-.50810197 0-.92-.41189803-.92-.92 0-.30020869.1464741-.58153499.39241464-.75369337l7.03554714-4.92488299c.34432015-.2410241.80260453-.2410241 1.14692468 0zm-.57346234 2.03988748-3.65526982 2.55868888h7.31053962z" fill-rule="evenodd"/></symbol><symbol id="icon-account" viewBox="0 0 18 18"><path d="m10.2379028 16.9048051c1.3083556-.2032362 2.5118471-.7235183 3.5294683-1.4798399-.8731327-2.5141501-2.0638925-3.935978-3.7673711-4.3188248v-1.27684611c1.1651924-.41183641 2-1.52307546 2-2.82929429 0-1.65685425-1.3431458-3-3-3-1.65685425 0-3 1.34314575-3 3 0 1.30621883.83480763 2.41745788 2 2.82929429v1.27684611c-1.70347856.3828468-2.89423845 1.8046747-3.76737114 4.3188248 1.01762123.7563216 2.22111275 1.2766037 3.52946833 1.4798399.40563808.0629726.81921174.0951949 1.23790281.0951949s.83226473-.0322223 1.2379028-.0951949zm4.3421782-2.1721994c1.4927655-1.4532925 2.419919-3.484675 2.419919-5.7326057 0-4.418278-3.581722-8-8-8s-8 3.581722-8 8c0 2.2479307.92715352 4.2793132 2.41991895 5.7326057.75688473-2.0164459 1.83949951-3.6071894 3.48926591-4.3218837-1.14534283-.70360829-1.90918486-1.96796271-1.90918486-3.410722 0-2.209139 1.790861-4 4-4s4 1.790861 4 4c0 1.44275929-.763842 2.70711371-1.9091849 3.410722 1.6497664.7146943 2.7323812 2.3054378 3.4892659 4.3218837zm-5.580081 3.2673943c-4.97056275 0-9-4.0294373-9-9 0-4.97056275 4.02943725-9 9-9 4.9705627 0 9 4.02943725 9 9 0 4.9705627-4.0294373 9-9 9z" fill-rule="evenodd"/></symbol><symbol id="icon-alert" viewBox="0 0 18 18"><path d="m4 10h2.5c.27614237 0 .5.2238576.5.5s-.22385763.5-.5.5h-3.08578644l-1.12132034 1.1213203c-.18753638.1875364-.29289322.4418903-.29289322.7071068v.1715729h14v-.1715729c0-.2652165-.1053568-.5195704-.2928932-.7071068l-1.7071068-1.7071067v-3.4142136c0-2.76142375-2.2385763-5-5-5-2.76142375 0-5 2.23857625-5 5zm3 4c0 1.1045695.8954305 2 2 2s2-.8954305 2-2zm-5 0c-.55228475 0-1-.4477153-1-1v-.1715729c0-.530433.21071368-1.0391408.58578644-1.4142135l1.41421356-1.4142136v-3c0-3.3137085 2.6862915-6 6-6s6 2.6862915 6 6v3l1.4142136 1.4142136c.3750727.3750727.5857864.8837805.5857864 1.4142135v.1715729c0 .5522847-.4477153 1-1 1h-4c0 1.6568542-1.3431458 3-3 3-1.65685425 0-3-1.3431458-3-3z" fill-rule="evenodd"/></symbol><symbol id="icon-arrow-broad" viewBox="0 0 16 16"><path d="m6.10307866 2.97190702v7.69043288l2.44965196-2.44676915c.38776071-.38730439 1.0088052-.39493524 1.38498697-.01919617.38609051.38563612.38643641 1.01053024-.00013864 1.39665039l-4.12239817 4.11754683c-.38616704.3857126-1.01187344.3861062-1.39846576-.0000311l-4.12258206-4.11773056c-.38618426-.38572979-.39254614-1.00476697-.01636437-1.38050605.38609047-.38563611 1.01018509-.38751562 1.4012233.00306241l2.44985644 2.4469734v-8.67638639c0-.54139983.43698413-.98042709.98493125-.98159081l7.89910522-.0043627c.5451687 0 .9871152.44142642.9871152.98595351s-.4419465.98595351-.9871152.98595351z" fill-rule="evenodd" transform="matrix(-1 0 0 -1 14 15)"/></symbol><symbol id="icon-arrow-down" viewBox="0 0 16 16"><path d="m3.28337502 11.5302405 4.03074001 4.176208c.37758093.3912076.98937525.3916069 1.367372-.0000316l4.03091977-4.1763942c.3775978-.3912252.3838182-1.0190815.0160006-1.4001736-.3775061-.39113013-.9877245-.39303641-1.3700683.003106l-2.39538585 2.4818345v-11.6147896l-.00649339-.11662112c-.055753-.49733869-.46370161-.88337888-.95867408-.88337888-.49497246 0-.90292107.38604019-.95867408.88337888l-.00649338.11662112v11.6147896l-2.39518594-2.4816273c-.37913917-.39282218-.98637524-.40056175-1.35419292-.0194697-.37750607.3911302-.37784433 1.0249269.00013556 1.4165479z" fill-rule="evenodd"/></symbol><symbol id="icon-arrow-left" viewBox="0 0 16 16"><path d="m4.46975946 3.28337502-4.17620792 4.03074001c-.39120768.37758093-.39160691.98937525.0000316 1.367372l4.1763942 4.03091977c.39122514.3775978 1.01908149.3838182 1.40017357.0160006.39113012-.3775061.3930364-.9877245-.00310603-1.3700683l-2.48183446-2.39538585h11.61478958l.1166211-.00649339c.4973387-.055753.8833789-.46370161.8833789-.95867408 0-.49497246-.3860402-.90292107-.8833789-.95867408l-.1166211-.00649338h-11.61478958l2.4816273-2.39518594c.39282216-.37913917.40056173-.98637524.01946965-1.35419292-.39113012-.37750607-1.02492687-.37784433-1.41654791.00013556z" fill-rule="evenodd"/></symbol><symbol id="icon-arrow-right" viewBox="0 0 16 16"><path d="m11.5302405 12.716625 4.176208-4.03074003c.3912076-.37758093.3916069-.98937525-.0000316-1.367372l-4.1763942-4.03091981c-.3912252-.37759778-1.0190815-.38381821-1.4001736-.01600053-.39113013.37750607-.39303641.98772445.003106 1.37006824l2.4818345 2.39538588h-11.6147896l-.11662112.00649339c-.49733869.055753-.88337888.46370161-.88337888.95867408 0 .49497246.38604019.90292107.88337888.95867408l.11662112.00649338h11.6147896l-2.4816273 2.39518592c-.39282218.3791392-.40056175.9863753-.0194697 1.3541929.3911302.3775061 1.0249269.3778444 1.4165479-.0001355z" fill-rule="evenodd"/></symbol><symbol id="icon-arrow-sub" viewBox="0 0 16 16"><path d="m7.89692134 4.97190702v7.69043288l-2.44965196-2.4467692c-.38776071-.38730434-1.0088052-.39493519-1.38498697-.0191961-.38609047.3856361-.38643643 1.0105302.00013864 1.3966504l4.12239817 4.1175468c.38616704.3857126 1.01187344.3861062 1.39846576-.0000311l4.12258202-4.1177306c.3861843-.3857298.3925462-1.0047669.0163644-1.380506-.3860905-.38563612-1.0101851-.38751563-1.4012233.0030624l-2.44985643 2.4469734v-8.67638639c0-.54139983-.43698413-.98042709-.98493125-.98159081l-7.89910525-.0043627c-.54516866 0-.98711517.44142642-.98711517.98595351s.44194651.98595351.98711517.98595351z" fill-rule="evenodd"/></symbol><symbol id="icon-arrow-up" viewBox="0 0 16 16"><path d="m12.716625 4.46975946-4.03074003-4.17620792c-.37758093-.39120768-.98937525-.39160691-1.367372.0000316l-4.03091981 4.1763942c-.37759778.39122514-.38381821 1.01908149-.01600053 1.40017357.37750607.39113012.98772445.3930364 1.37006824-.00310603l2.39538588-2.48183446v11.61478958l.00649339.1166211c.055753.4973387.46370161.8833789.95867408.8833789.49497246 0 .90292107-.3860402.95867408-.8833789l.00649338-.1166211v-11.61478958l2.39518592 2.4816273c.3791392.39282216.9863753.40056173 1.3541929.01946965.3775061-.39113012.3778444-1.02492687-.0001355-1.41654791z" fill-rule="evenodd"/></symbol><symbol id="icon-article" viewBox="0 0 18 18"><path d="m13 15v-12.9906311c0-.0073595-.0019884-.0093689.0014977-.0093689l-11.00158888.00087166v13.00506804c0 .5482678.44615281.9940603.99415146.9940603h10.27350412c-.1701701-.2941734-.2675644-.6357129-.2675644-1zm-12 .0059397v-13.00506804c0-.5562408.44704472-1.00087166.99850233-1.00087166h11.00299537c.5510129 0 .9985023.45190985.9985023 1.0093689v2.9906311h3v9.9914698c0 1.1065798-.8927712 2.0085302-1.9940603 2.0085302h-12.01187942c-1.09954652 0-1.99406028-.8927712-1.99406028-1.9940603zm13-9.0059397v9c0 .5522847.4477153 1 1 1s1-.4477153 1-1v-9zm-10-2h7v4h-7zm1 1v2h5v-2zm-1 4h7v1h-7zm0 2h7v1h-7zm0 2h7v1h-7z" fill-rule="evenodd"/></symbol><symbol id="icon-audio" viewBox="0 0 18 18"><path d="m13.0957477 13.5588459c-.195279.1937043-.5119137.193729-.7072234.0000551-.1953098-.193674-.1953346-.5077061-.0000556-.7014104 1.0251004-1.0168342 1.6108711-2.3905226 1.6108711-3.85745208 0-1.46604976-.5850634-2.83898246-1.6090736-3.85566829-.1951894-.19379323-.1950192-.50782531.0003802-.70141028.1953993-.19358497.512034-.19341614.7072234.00037709 1.2094886 1.20083761 1.901635 2.8250555 1.901635 4.55670148 0 1.73268608-.6929822 3.35779608-1.9037571 4.55880738zm2.1233994 2.1025159c-.195234.193749-.5118687.1938462-.7072235.0002171-.1953548-.1936292-.1954528-.5076613-.0002189-.7014104 1.5832215-1.5711805 2.4881302-3.6939808 2.4881302-5.96012998 0-2.26581266-.9046382-4.3883241-2.487443-5.95944795-.1952117-.19377107-.1950777-.50780316.0002993-.70141031s.5120117-.19347426.7072234.00029682c1.7683321 1.75528196 2.7800854 4.12911258 2.7800854 6.66056144 0 2.53182498-1.0120556 4.90597838-2.7808529 6.66132328zm-14.21898205-3.6854911c-.5523759 0-1.00016505-.4441085-1.00016505-.991944v-3.96777631c0-.54783558.44778915-.99194407 1.00016505-.99194407h2.0003301l5.41965617-3.8393633c.44948677-.31842296 1.07413994-.21516983 1.39520191.23062232.12116339.16823446.18629727.36981184.18629727.57655577v12.01603479c0 .5478356-.44778914.9919441-1.00016505.9919441-.20845738 0-.41170538-.0645985-.58133413-.184766l-5.41965617-3.8393633zm0-.991944h2.32084805l5.68047235 4.0241292v-12.01603479l-5.68047235 4.02412928h-2.32084805z" fill-rule="evenodd"/></symbol><symbol id="icon-block" viewBox="0 0 24 24"><path d="m0 0h24v24h-24z" fill-rule="evenodd"/></symbol><symbol id="icon-book" viewBox="0 0 18 18"><path d="m4 13v-11h1v11h11v-11h-13c-.55228475 0-1 .44771525-1 1v10.2675644c.29417337-.1701701.63571286-.2675644 1-.2675644zm12 1h-13c-.55228475 0-1 .4477153-1 1s.44771525 1 1 1h13zm0 3h-13c-1.1045695 0-2-.8954305-2-2v-12c0-1.1045695.8954305-2 2-2h13c.5522847 0 1 .44771525 1 1v14c0 .5522847-.4477153 1-1 1zm-8.5-13h6c.2761424 0 .5.22385763.5.5s-.2238576.5-.5.5h-6c-.27614237 0-.5-.22385763-.5-.5s.22385763-.5.5-.5zm1 2h4c.2761424 0 .5.22385763.5.5s-.2238576.5-.5.5h-4c-.27614237 0-.5-.22385763-.5-.5s.22385763-.5.5-.5z" fill-rule="evenodd"/></symbol><symbol id="icon-broad" viewBox="0 0 24 24"><path d="m9.18274226 7.81v7.7999954l2.48162734-2.4816273c.3928221-.3928221 1.0219731-.4005617 1.4030652-.0194696.3911301.3911301.3914806 1.0249268-.0001404 1.4165479l-4.17620796 4.1762079c-.39120769.3912077-1.02508144.3916069-1.41671995-.0000316l-4.1763942-4.1763942c-.39122514-.3912251-.39767006-1.0190815-.01657798-1.4001736.39113012-.3911301 1.02337106-.3930364 1.41951349.0031061l2.48183446 2.4818344v-8.7999954c0-.54911294.4426881-.99439484.99778758-.99557515l8.00221246-.00442485c.5522847 0 1 .44771525 1 1s-.4477153 1-1 1z" fill-rule="evenodd" transform="matrix(-1 0 0 -1 20.182742 24.805206)"/></symbol><symbol id="icon-calendar" viewBox="0 0 18 18"><path d="m12.5 0c.2761424 0 .5.21505737.5.49047852v.50952148h2c1.1072288 0 2 .89451376 2 2v12c0 1.1072288-.8945138 2-2 2h-12c-1.1072288 0-2-.8945138-2-2v-12c0-1.1072288.89451376-2 2-2h1v1h-1c-.55393837 0-1 .44579254-1 1v3h14v-3c0-.55393837-.4457925-1-1-1h-2v1.50952148c0 .27088381-.2319336.49047852-.5.49047852-.2761424 0-.5-.21505737-.5-.49047852v-3.01904296c0-.27088381.2319336-.49047852.5-.49047852zm3.5 7h-14v8c0 .5539384.44579254 1 1 1h12c.5539384 0 1-.4457925 1-1zm-11 6v1h-1v-1zm3 0v1h-1v-1zm3 0v1h-1v-1zm-6-2v1h-1v-1zm3 0v1h-1v-1zm6 0v1h-1v-1zm-3 0v1h-1v-1zm-3-2v1h-1v-1zm6 0v1h-1v-1zm-3 0v1h-1v-1zm-5.5-9c.27614237 0 .5.21505737.5.49047852v.50952148h5v1h-5v1.50952148c0 .27088381-.23193359.49047852-.5.49047852-.27614237 0-.5-.21505737-.5-.49047852v-3.01904296c0-.27088381.23193359-.49047852.5-.49047852z" fill-rule="evenodd"/></symbol><symbol id="icon-cart" viewBox="0 0 18 18"><path d="m5 14c1.1045695 0 2 .8954305 2 2s-.8954305 2-2 2-2-.8954305-2-2 .8954305-2 2-2zm10 0c1.1045695 0 2 .8954305 2 2s-.8954305 2-2 2-2-.8954305-2-2 .8954305-2 2-2zm-10 1c-.55228475 0-1 .4477153-1 1s.44771525 1 1 1 1-.4477153 1-1-.44771525-1-1-1zm10 0c-.5522847 0-1 .4477153-1 1s.4477153 1 1 1 1-.4477153 1-1-.4477153-1-1-1zm-12.82032249-15c.47691417 0 .88746157.33678127.98070211.80449199l.23823144 1.19501025 13.36277974.00045554c.5522847.00001882.9999659.44774934.9999659 1.00004222 0 .07084994-.0075361.14150708-.022474.2107727l-1.2908094 5.98534344c-.1007861.46742419-.5432548.80388386-1.0571651.80388386h-10.24805106c-.59173366 0-1.07142857.4477153-1.07142857 1 0 .5128358.41361449.9355072.94647737.9932723l.1249512.0067277h10.35933776c.2749512 0 .4979349.2228539.4979349.4978051 0 .2749417-.2227336.4978951-.4976753.4980063l-10.35959736.0041886c-1.18346732 0-2.14285714-.8954305-2.14285714-2 0-.6625717.34520317-1.24989198.87690425-1.61383592l-1.63768102-8.19004794c-.01312273-.06561364-.01950005-.131011-.0196107-.19547395l-1.71961253-.00064219c-.27614237 0-.5-.22385762-.5-.5 0-.27614237.22385763-.5.5-.5zm14.53193359 2.99950224h-13.11300004l1.20580469 6.02530174c.11024034-.0163252.22327998-.02480398.33844139-.02480398h10.27064786z"/></symbol><symbol id="icon-chevron-less" viewBox="0 0 10 10"><path d="m5.58578644 4-3.29289322-3.29289322c-.39052429-.39052429-.39052429-1.02368927 0-1.41421356s1.02368927-.39052429 1.41421356 0l4 4c.39052429.39052429.39052429 1.02368927 0 1.41421356l-4 4c-.39052429.39052429-1.02368927.39052429-1.41421356 0s-.39052429-1.02368927 0-1.41421356z" fill-rule="evenodd" transform="matrix(0 -1 -1 0 9 9)"/></symbol><symbol id="icon-chevron-more" viewBox="0 0 10 10"><path d="m5.58578644 6-3.29289322-3.29289322c-.39052429-.39052429-.39052429-1.02368927 0-1.41421356s1.02368927-.39052429 1.41421356 0l4 4c.39052429.39052429.39052429 1.02368927 0 1.41421356l-4 4.00000002c-.39052429.3905243-1.02368927.3905243-1.41421356 0s-.39052429-1.02368929 0-1.41421358z" fill-rule="evenodd" transform="matrix(0 1 -1 0 11 1)"/></symbol><symbol id="icon-chevron-right" viewBox="0 0 10 10"><path d="m5.96738168 4.70639573 2.39518594-2.41447274c.37913917-.38219212.98637524-.38972225 1.35419292-.01894278.37750606.38054586.37784436.99719163-.00013556 1.37821513l-4.03074001 4.06319683c-.37758093.38062133-.98937525.38100976-1.367372-.00003075l-4.03091981-4.06337806c-.37759778-.38063832-.38381821-.99150444-.01600053-1.3622839.37750607-.38054587.98772445-.38240057 1.37006824.00302197l2.39538588 2.4146743.96295325.98624457z" fill-rule="evenodd" transform="matrix(0 -1 1 0 0 10)"/></symbol><symbol id="icon-circle-fill" viewBox="0 0 16 16"><path d="m8 14c-3.3137085 0-6-2.6862915-6-6s2.6862915-6 6-6 6 2.6862915 6 6-2.6862915 6-6 6z" fill-rule="evenodd"/></symbol><symbol id="icon-circle" viewBox="0 0 16 16"><path d="m8 12c2.209139 0 4-1.790861 4-4s-1.790861-4-4-4-4 1.790861-4 4 1.790861 4 4 4zm0 2c-3.3137085 0-6-2.6862915-6-6s2.6862915-6 6-6 6 2.6862915 6 6-2.6862915 6-6 6z" fill-rule="evenodd"/></symbol><symbol id="icon-citation" viewBox="0 0 18 18"><path d="m8.63593473 5.99995183c2.20913897 0 3.99999997 1.79084375 3.99999997 3.99996146 0 1.40730761-.7267788 2.64486871-1.8254829 3.35783281 1.6240224.6764218 2.8754442 2.0093871 3.4610603 3.6412466l-1.0763845.000006c-.5310008-1.2078237-1.5108121-2.1940153-2.7691712-2.7181346l-.79002167-.329052v-1.023992l.63016577-.4089232c.8482885-.5504661 1.3698342-1.4895187 1.3698342-2.51898361 0-1.65683828-1.3431457-2.99996146-2.99999997-2.99996146-1.65685425 0-3 1.34312318-3 2.99996146 0 1.02946491.52154569 1.96851751 1.36983419 2.51898361l.63016581.4089232v1.023992l-.79002171.329052c-1.25835905.5241193-2.23817037 1.5103109-2.76917113 2.7181346l-1.07638453-.000006c.58561612-1.6318595 1.8370379-2.9648248 3.46106024-3.6412466-1.09870405-.7129641-1.82548287-1.9505252-1.82548287-3.35783281 0-2.20911771 1.790861-3.99996146 4-3.99996146zm7.36897597-4.99995183c1.1018574 0 1.9950893.89353404 1.9950893 2.00274083v5.994422c0 1.10608317-.8926228 2.00274087-1.9950893 2.00274087l-3.0049107-.0009037v-1l3.0049107.00091329c.5490631 0 .9950893-.44783123.9950893-1.00275046v-5.994422c0-.55646537-.4450595-1.00275046-.9950893-1.00275046h-14.00982141c-.54906309 0-.99508929.44783123-.99508929 1.00275046v5.9971821c0 .66666024.33333333.99999036 1 .99999036l2-.00091329v1l-2 .0009037c-1 0-2-.99999041-2-1.99998077v-5.9971821c0-1.10608322.8926228-2.00274083 1.99508929-2.00274083zm-8.5049107 2.9999711c.27614237 0 .5.22385547.5.5 0 .2761349-.22385763.5-.5.5h-4c-.27614237 0-.5-.2238651-.5-.5 0-.27614453.22385763-.5.5-.5zm3 0c.2761424 0 .5.22385547.5.5 0 .2761349-.2238576.5-.5.5h-1c-.27614237 0-.5-.2238651-.5-.5 0-.27614453.22385763-.5.5-.5zm4 0c.2761424 0 .5.22385547.5.5 0 .2761349-.2238576.5-.5.5h-2c-.2761424 0-.5-.2238651-.5-.5 0-.27614453.2238576-.5.5-.5z" fill-rule="evenodd"/></symbol><symbol id="icon-close" viewBox="0 0 16 16"><path d="m2.29679575 12.2772478c-.39658757.3965876-.39438847 1.0328109-.00062148 1.4265779.39651227.3965123 1.03246768.3934888 1.42657791-.0006214l4.27724782-4.27724787 4.2772478 4.27724787c.3965876.3965875 1.0328109.3943884 1.4265779.0006214.3965123-.3965122.3934888-1.0324677-.0006214-1.4265779l-4.27724787-4.2772478 4.27724787-4.27724782c.3965875-.39658757.3943884-1.03281091.0006214-1.42657791-.3965122-.39651226-1.0324677-.39348875-1.4265779.00062148l-4.2772478 4.27724782-4.27724782-4.27724782c-.39658757-.39658757-1.03281091-.39438847-1.42657791-.00062148-.39651226.39651227-.39348875 1.03246768.00062148 1.42657791l4.27724782 4.27724782z" fill-rule="evenodd"/></symbol><symbol id="icon-collections" viewBox="0 0 18 18"><path d="m15 4c1.1045695 0 2 .8954305 2 2v9c0 1.1045695-.8954305 2-2 2h-8c-1.1045695 0-2-.8954305-2-2h1c0 .5128358.38604019.9355072.88337887.9932723l.11662113.0067277h8c.5128358 0 .9355072-.3860402.9932723-.8833789l.0067277-.1166211v-9c0-.51283584-.3860402-.93550716-.8833789-.99327227l-.1166211-.00672773h-1v-1zm-4-3c1.1045695 0 2 .8954305 2 2v9c0 1.1045695-.8954305 2-2 2h-8c-1.1045695 0-2-.8954305-2-2v-9c0-1.1045695.8954305-2 2-2zm0 1h-8c-.51283584 0-.93550716.38604019-.99327227.88337887l-.00672773.11662113v9c0 .5128358.38604019.9355072.88337887.9932723l.11662113.0067277h8c.5128358 0 .9355072-.3860402.9932723-.8833789l.0067277-.1166211v-9c0-.51283584-.3860402-.93550716-.8833789-.99327227zm-1.5 7c.27614237 0 .5.22385763.5.5s-.22385763.5-.5.5h-5c-.27614237 0-.5-.22385763-.5-.5s.22385763-.5.5-.5zm0-2c.27614237 0 .5.22385763.5.5s-.22385763.5-.5.5h-5c-.27614237 0-.5-.22385763-.5-.5s.22385763-.5.5-.5zm0-2c.27614237 0 .5.22385763.5.5s-.22385763.5-.5.5h-5c-.27614237 0-.5-.22385763-.5-.5s.22385763-.5.5-.5z" fill-rule="evenodd"/></symbol><symbol id="icon-compare" viewBox="0 0 18 18"><path d="m12 3c3.3137085 0 6 2.6862915 6 6s-2.6862915 6-6 6c-1.0928452 0-2.11744941-.2921742-2.99996061-.8026704-.88181407.5102749-1.90678042.8026704-3.00003939.8026704-3.3137085 0-6-2.6862915-6-6s2.6862915-6 6-6c1.09325897 0 2.11822532.29239547 3.00096303.80325037.88158756-.51107621 1.90619177-.80325037 2.99903697-.80325037zm-6 1c-2.76142375 0-5 2.23857625-5 5 0 2.7614237 2.23857625 5 5 5 .74397391 0 1.44999672-.162488 2.08451611-.4539116-1.27652344-1.1000812-2.08451611-2.7287264-2.08451611-4.5460884s.80799267-3.44600721 2.08434391-4.5463015c-.63434719-.29121054-1.34037-.4536985-2.08434391-.4536985zm6 0c-.7439739 0-1.4499967.16248796-2.08451611.45391156 1.27652341 1.10008123 2.08451611 2.72872644 2.08451611 4.54608844s-.8079927 3.4460072-2.08434391 4.5463015c.63434721.2912105 1.34037001.4536985 2.08434391.4536985 2.7614237 0 5-2.2385763 5-5 0-2.76142375-2.2385763-5-5-5zm-1.4162763 7.0005324h-3.16744736c.15614659.3572676.35283837.6927622.58425872 1.0006671h1.99892988c.23142036-.3079049.42811216-.6433995.58425876-1.0006671zm.4162763-2.0005324h-4c0 .34288501.0345146.67770871.10025909 1.0011864h3.79948181c.0657445-.32347769.1002591-.65830139.1002591-1.0011864zm-.4158423-1.99953894h-3.16831543c-.13859957.31730812-.24521946.651783-.31578599.99935097h3.79988742c-.0705665-.34756797-.1771864-.68204285-.315786-.99935097zm-1.58295822-1.999926-.08316107.06199199c-.34550042.27081213-.65446126.58611297-.91825862.93727862h2.00044041c-.28418626-.37830727-.6207872-.71499149-.99902072-.99927061z" fill-rule="evenodd"/></symbol><symbol id="icon-download-file" viewBox="0 0 18 18"><path d="m10.0046024 0c.5497429 0 1.3179837.32258606 1.707238.71184039l4.5763192 4.57631922c.3931386.39313859.7118404 1.16760135.7118404 1.71431368v8.98899651c0 1.1092806-.8945138 2.0085302-1.9940603 2.0085302h-12.01187942c-1.10128908 0-1.99406028-.8926228-1.99406028-1.9950893v-14.00982141c0-1.10185739.88743329-1.99508929 1.99961498-1.99508929zm0 1h-7.00498742c-.55709576 0-.99961498.44271433-.99961498.99508929v14.00982141c0 .5500396.44491393.9950893.99406028.9950893h12.01187942c.5463747 0 .9940603-.4506622.9940603-1.0085302v-8.98899651c0-.28393444-.2150684-.80332809-.4189472-1.0072069l-4.5763192-4.57631922c-.2038461-.20384606-.718603-.41894717-1.0001312-.41894717zm-1.5046024 4c.27614237 0 .5.21637201.5.49209595v6.14827645l1.7462789-1.77990922c.1933927-.1971171.5125222-.19455839.7001689-.0069117.1932998.19329992.1910058.50899492-.0027774.70277812l-2.59089271 2.5908927c-.19483374.1948337-.51177825.1937771-.70556873-.0000133l-2.59099079-2.5909908c-.19484111-.1948411-.19043735-.5151448-.00279066-.70279146.19329987-.19329987.50465175-.19237083.70018565.00692852l1.74638684 1.78001764v-6.14827695c0-.27177709.23193359-.49209595.5-.49209595z" fill-rule="evenodd"/></symbol><symbol id="icon-download" viewBox="0 0 16 16"><path d="m12.9975267 12.999368c.5467123 0 1.0024733.4478567 1.0024733 1.000316 0 .5563109-.4488226 1.000316-1.0024733 1.000316h-9.99505341c-.54671233 0-1.00247329-.4478567-1.00247329-1.000316 0-.5563109.44882258-1.000316 1.00247329-1.000316zm-4.9975267-11.999368c.55228475 0 1 .44497754 1 .99589209v6.80214418l2.4816273-2.48241149c.3928222-.39294628 1.0219732-.4006883 1.4030652-.01947579.3911302.39125371.3914806 1.02525073-.0001404 1.41699553l-4.17620792 4.17752758c-.39120769.3913313-1.02508144.3917306-1.41671995-.0000316l-4.17639421-4.17771394c-.39122513-.39134876-.39767006-1.01940351-.01657797-1.40061601.39113012-.39125372 1.02337105-.3931606 1.41951349.00310701l2.48183446 2.48261871v-6.80214418c0-.55001601.44386482-.99589209 1-.99589209z" fill-rule="evenodd"/></symbol><symbol id="icon-editors" viewBox="0 0 18 18"><path d="m8.72592184 2.54588137c-.48811714-.34391207-1.08343326-.54588137-1.72592184-.54588137-1.65685425 0-3 1.34314575-3 3 0 1.02947485.5215457 1.96853646 1.3698342 2.51900785l.6301658.40892721v1.02400182l-.79002171.32905522c-1.93395773.8055207-3.20997829 2.7024791-3.20997829 4.8180274v.9009805h-1v-.9009805c0-2.5479714 1.54557359-4.79153984 3.82548288-5.7411543-1.09870406-.71297106-1.82548288-1.95054399-1.82548288-3.3578652 0-2.209139 1.790861-4 4-4 1.09079823 0 2.07961816.43662103 2.80122451 1.1446278-.37707584.09278571-.7373238.22835063-1.07530267.40125357zm-2.72592184 14.45411863h-1v-.9009805c0-2.5479714 1.54557359-4.7915398 3.82548288-5.7411543-1.09870406-.71297106-1.82548288-1.95054399-1.82548288-3.3578652 0-2.209139 1.790861-4 4-4s4 1.790861 4 4c0 1.40732121-.7267788 2.64489414-1.8254829 3.3578652 2.2799093.9496145 3.8254829 3.1931829 3.8254829 5.7411543v.9009805h-1v-.9009805c0-2.1155483-1.2760206-4.0125067-3.2099783-4.8180274l-.7900217-.3290552v-1.02400184l.6301658-.40892721c.8482885-.55047139 1.3698342-1.489533 1.3698342-2.51900785 0-1.65685425-1.3431458-3-3-3-1.65685425 0-3 1.34314575-3 3 0 1.02947485.5215457 1.96853646 1.3698342 2.51900785l.6301658.40892721v1.02400184l-.79002171.3290552c-1.93395773.8055207-3.20997829 2.7024791-3.20997829 4.8180274z" fill-rule="evenodd"/></symbol><symbol id="icon-email" viewBox="0 0 18 18"><path d="m16.0049107 2c1.1018574 0 1.9950893.89706013 1.9950893 2.00585866v9.98828264c0 1.1078052-.8926228 2.0058587-1.9950893 2.0058587h-14.00982141c-1.10185739 0-1.99508929-.8970601-1.99508929-2.0058587v-9.98828264c0-1.10780515.8926228-2.00585866 1.99508929-2.00585866zm0 1h-14.00982141c-.54871518 0-.99508929.44887827-.99508929 1.00585866v9.98828264c0 .5572961.44630695 1.0058587.99508929 1.0058587h14.00982141c.5487152 0 .9950893-.4488783.9950893-1.0058587v-9.98828264c0-.55729607-.446307-1.00585866-.9950893-1.00585866zm-.0049107 2.55749512v1.44250488l-7 4-7-4v-1.44250488l7 4z" fill-rule="evenodd"/></symbol><symbol id="icon-error" viewBox="0 0 18 18"><path d="m9 0c4.9705627 0 9 4.02943725 9 9 0 4.9705627-4.0294373 9-9 9-4.97056275 0-9-4.0294373-9-9 0-4.97056275 4.02943725-9 9-9zm2.8630343 4.71100931-2.8630343 2.86303426-2.86303426-2.86303426c-.39658757-.39658757-1.03281091-.39438847-1.4265779-.00062147-.39651227.39651226-.39348876 1.03246767.00062147 1.4265779l2.86303426 2.86303426-2.86303426 2.8630343c-.39658757.3965875-.39438847 1.0328109-.00062147 1.4265779.39651226.3965122 1.03246767.3934887 1.4265779-.0006215l2.86303426-2.8630343 2.8630343 2.8630343c.3965875.3965876 1.0328109.3943885 1.4265779.0006215.3965122-.3965123.3934887-1.0324677-.0006215-1.4265779l-2.8630343-2.8630343 2.8630343-2.86303426c.3965876-.39658757.3943885-1.03281091.0006215-1.4265779-.3965123-.39651227-1.0324677-.39348876-1.4265779.00062147z" fill-rule="evenodd"/></symbol><symbol id="icon-ethics" viewBox="0 0 18 18"><path d="m6.76384967 1.41421356.83301651-.8330165c.77492941-.77492941 2.03133823-.77492941 2.80626762 0l.8330165.8330165c.3750728.37507276.8837806.58578644 1.4142136.58578644h1.3496361c1.1045695 0 2 .8954305 2 2v1.34963611c0 .53043298.2107137 1.03914081.5857864 1.41421356l.8330165.83301651c.7749295.77492941.7749295 2.03133823 0 2.80626762l-.8330165.8330165c-.3750727.3750728-.5857864.8837806-.5857864 1.4142136v1.3496361c0 1.1045695-.8954305 2-2 2h-1.3496361c-.530433 0-1.0391408.2107137-1.4142136.5857864l-.8330165.8330165c-.77492939.7749295-2.03133821.7749295-2.80626762 0l-.83301651-.8330165c-.37507275-.3750727-.88378058-.5857864-1.41421356-.5857864h-1.34963611c-1.1045695 0-2-.8954305-2-2v-1.3496361c0-.530433-.21071368-1.0391408-.58578644-1.4142136l-.8330165-.8330165c-.77492941-.77492939-.77492941-2.03133821 0-2.80626762l.8330165-.83301651c.37507276-.37507275.58578644-.88378058.58578644-1.41421356v-1.34963611c0-1.1045695.8954305-2 2-2h1.34963611c.53043298 0 1.03914081-.21071368 1.41421356-.58578644zm-1.41421356 1.58578644h-1.34963611c-.55228475 0-1 .44771525-1 1v1.34963611c0 .79564947-.31607052 1.55871121-.87867966 2.12132034l-.8330165.83301651c-.38440512.38440512-.38440512 1.00764896 0 1.39205408l.8330165.83301646c.56260914.5626092.87867966 1.3256709.87867966 2.1213204v1.3496361c0 .5522847.44771525 1 1 1h1.34963611c.79564947 0 1.55871121.3160705 2.12132034.8786797l.83301651.8330165c.38440512.3844051 1.00764896.3844051 1.39205408 0l.83301646-.8330165c.5626092-.5626092 1.3256709-.8786797 2.1213204-.8786797h1.3496361c.5522847 0 1-.4477153 1-1v-1.3496361c0-.7956495.3160705-1.5587112.8786797-2.1213204l.8330165-.83301646c.3844051-.38440512.3844051-1.00764896 0-1.39205408l-.8330165-.83301651c-.5626092-.56260913-.8786797-1.32567087-.8786797-2.12132034v-1.34963611c0-.55228475-.4477153-1-1-1h-1.3496361c-.7956495 0-1.5587112-.31607052-2.1213204-.87867966l-.83301646-.8330165c-.38440512-.38440512-1.00764896-.38440512-1.39205408 0l-.83301651.8330165c-.56260913.56260914-1.32567087.87867966-2.12132034.87867966zm3.58698944 11.4960218c-.02081224.002155-.04199226.0030286-.06345763.002542-.98766446-.0223875-1.93408568-.3063547-2.75885125-.8155622-.23496767-.1450683-.30784554-.4531483-.16277726-.688116.14506827-.2349677.45314827-.3078455.68811595-.1627773.67447084.4164161 1.44758575.6483839 2.25617384.6667123.01759529.0003988.03495764.0017019.05204365.0038639.01713363-.0017748.03452416-.0026845.05212715-.0026845 2.4852814 0 4.5-2.0147186 4.5-4.5 0-1.04888973-.3593547-2.04134635-1.0074477-2.83787157-.1742817-.21419731-.1419238-.5291218.0722736-.70340353.2141973-.17428173.5291218-.14192375.7034035.07227357.7919032.97327203 1.2317706 2.18808682 1.2317706 3.46900153 0 3.0375661-2.4624339 5.5-5.5 5.5-.02146768 0-.04261937-.0013529-.06337445-.0039782zm1.57975095-10.78419583c.2654788.07599731.419084.35281842.3430867.61829728-.0759973.26547885-.3528185.419084-.6182973.3430867-.37560116-.10752146-.76586237-.16587951-1.15568824-.17249193-2.5587807-.00064534-4.58547766 2.00216524-4.58547766 4.49928198 0 .62691557.12797645 1.23496.37274865 1.7964426.11035133.2531347-.0053975.5477984-.25853224.6581497-.25313473.1103514-.54779841-.0053975-.65814974-.2585322-.29947131-.6869568-.45606667-1.43097603-.45606667-2.1960601 0-3.05211432 2.47714695-5.50006595 5.59399617-5.49921198.48576182.00815502.96289603.0795037 1.42238033.21103795zm-1.9766658 6.41091303 2.69835-2.94655317c.1788432-.21040373.4943901-.23598862.7047939-.05714545.2104037.17884318.2359886.49439014.0571454.70479387l-3.01637681 3.34277395c-.18039088.1999106-.48669547.2210637-.69285412.0478478l-1.93095347-1.62240047c-.21213845-.17678204-.24080048-.49206439-.06401844-.70420284.17678204-.21213844.49206439-.24080048.70420284-.06401844z" fill-rule="evenodd"/></symbol><symbol id="icon-expand"><path d="M7.498 11.918a.997.997 0 0 0-.003-1.411.995.995 0 0 0-1.412-.003l-4.102 4.102v-3.51A1 1 0 0 0 .98 10.09.992.992 0 0 0 0 11.092V17c0 .554.448 1.002 1.002 1.002h5.907c.554 0 1.002-.45 1.002-1.003 0-.539-.45-.978-1.006-.978h-3.51zm3.005-5.835a.997.997 0 0 0 .003 1.412.995.995 0 0 0 1.411.003l4.103-4.103v3.51a1 1 0 0 0 1.001 1.006A.992.992 0 0 0 18 6.91V1.002A1 1 0 0 0 17 0h-5.907a1.003 1.003 0 0 0-1.002 1.003c0 .539.45.978 1.006.978h3.51z" fill-rule="evenodd"/></symbol><symbol id="icon-explore" viewBox="0 0 18 18"><path d="m9 17c4.418278 0 8-3.581722 8-8s-3.581722-8-8-8-8 3.581722-8 8 3.581722 8 8 8zm0 1c-4.97056275 0-9-4.0294373-9-9 0-4.97056275 4.02943725-9 9-9 4.9705627 0 9 4.02943725 9 9 0 4.9705627-4.0294373 9-9 9zm0-2.5c-.27614237 0-.5-.2238576-.5-.5s.22385763-.5.5-.5c2.969509 0 5.400504-2.3575119 5.497023-5.31714844.0090007-.27599565.2400359-.49243782.5160315-.48343711.2759957.0090007.4924378.2400359.4834371.51603155-.114093 3.4985237-2.9869632 6.284554-6.4964916 6.284554zm-.29090657-12.99359748c.27587424-.01216621.50937715.20161139.52154336.47748563.01216621.27587423-.20161139.50937715-.47748563.52154336-2.93195733.12930094-5.25315116 2.54886451-5.25315116 5.49456849 0 .27614237-.22385763.5-.5.5s-.5-.22385763-.5-.5c0-3.48142406 2.74307146-6.34074398 6.20909343-6.49359748zm1.13784138 8.04763908-1.2004882-1.20048821c-.19526215-.19526215-.19526215-.51184463 0-.70710678s.51184463-.19526215.70710678 0l1.20048821 1.2004882 1.6006509-4.00162734-4.50670359 1.80268144-1.80268144 4.50670359zm4.10281269-6.50378907-2.6692597 6.67314927c-.1016411.2541026-.3029834.4554449-.557086.557086l-6.67314927 2.6692597 2.66925969-6.67314926c.10164107-.25410266.30298336-.45544495.55708602-.55708602z" fill-rule="evenodd"/></symbol><symbol id="icon-filter" viewBox="0 0 16 16"><path d="m14.9738641 0c.5667192 0 1.0261359.4477136 1.0261359 1 0 .24221858-.0902161.47620768-.2538899.65849851l-5.6938314 6.34147206v5.49997973c0 .3147562-.1520673.6111434-.4104543.7999971l-2.05227171 1.4999945c-.45337535.3313696-1.09655869.2418269-1.4365902-.1999993-.13321514-.1730955-.20522717-.3836284-.20522717-.5999978v-6.99997423l-5.69383133-6.34147206c-.3731872-.41563511-.32996891-1.0473954.09653074-1.41107611.18705584-.15950448.42716133-.2474224.67571519-.2474224zm-5.9218641 8.5h-2.105v6.491l.01238459.0070843.02053271.0015705.01955278-.0070558 2.0532976-1.4990996zm-8.02585008-7.5-.01564945.00240169 5.83249953 6.49759831h2.313l5.836-6.499z"/></symbol><symbol id="icon-home" viewBox="0 0 18 18"><path d="m9 5-6 6v5h4v-4h4v4h4v-5zm7 6.5857864v4.4142136c0 .5522847-.4477153 1-1 1h-5v-4h-2v4h-5c-.55228475 0-1-.4477153-1-1v-4.4142136c-.25592232 0-.51184464-.097631-.70710678-.2928932l-.58578644-.5857864c-.39052429-.3905243-.39052429-1.02368929 0-1.41421358l8.29289322-8.29289322 8.2928932 8.29289322c.3905243.39052429.3905243 1.02368928 0 1.41421358l-.5857864.5857864c-.1952622.1952622-.4511845.2928932-.7071068.2928932zm-7-9.17157284-7.58578644 7.58578644.58578644.5857864 7-6.99999996 7 6.99999996.5857864-.5857864z" fill-rule="evenodd"/></symbol><symbol id="icon-image" viewBox="0 0 18 18"><path d="m10.0046024 0c.5497429 0 1.3179837.32258606 1.707238.71184039l4.5763192 4.57631922c.3931386.39313859.7118404 1.16760135.7118404 1.71431368v8.98899651c0 1.1092806-.8945138 2.0085302-1.9940603 2.0085302h-12.01187942c-1.10128908 0-1.99406028-.8926228-1.99406028-1.9950893v-14.00982141c0-1.10185739.88743329-1.99508929 1.99961498-1.99508929zm-3.49645283 10.1752453-3.89407257 6.7495552c.11705545.048464.24538859.0751995.37998328.0751995h10.60290092l-2.4329715-4.2154691-1.57494129 2.7288098zm8.49779013 6.8247547c.5463747 0 .9940603-.4506622.9940603-1.0085302v-8.98899651c0-.28393444-.2150684-.80332809-.4189472-1.0072069l-4.5763192-4.57631922c-.2038461-.20384606-.718603-.41894717-1.0001312-.41894717h-7.00498742c-.55709576 0-.99961498.44271433-.99961498.99508929v13.98991071l4.50814957-7.81026689 3.08089884 5.33809539 1.57494129-2.7288097 3.5875735 6.2159812zm-3.0059397-11c1.1045695 0 2 .8954305 2 2s-.8954305 2-2 2-2-.8954305-2-2 .8954305-2 2-2zm0 1c-.5522847 0-1 .44771525-1 1s.4477153 1 1 1 1-.44771525 1-1-.4477153-1-1-1z" fill-rule="evenodd"/></symbol><symbol id="icon-info" viewBox="0 0 18 18"><path d="m9 0c4.9705627 0 9 4.02943725 9 9 0 4.9705627-4.0294373 9-9 9-4.97056275 0-9-4.0294373-9-9 0-4.97056275 4.02943725-9 9-9zm0 7h-1.5l-.11662113.00672773c-.49733868.05776511-.88337887.48043643-.88337887.99327227 0 .47338693.32893365.86994729.77070917.97358929l.1126697.01968298.11662113.00672773h.5v3h-.5l-.11662113.0067277c-.42082504.0488782-.76196299.3590206-.85696816.7639815l-.01968298.1126697-.00672773.1166211.00672773.1166211c.04887817.4208251.35902055.761963.76398144.8569682l.1126697.019683.11662113.0067277h3l.1166211-.0067277c.4973387-.0577651.8833789-.4804365.8833789-.9932723 0-.4733869-.3289337-.8699473-.7707092-.9735893l-.1126697-.019683-.1166211-.0067277h-.5v-4l-.00672773-.11662113c-.04887817-.42082504-.35902055-.76196299-.76398144-.85696816l-.1126697-.01968298zm0-3.25c-.69035594 0-1.25.55964406-1.25 1.25s.55964406 1.25 1.25 1.25 1.25-.55964406 1.25-1.25-.55964406-1.25-1.25-1.25z" fill-rule="evenodd"/></symbol><symbol id="icon-institution" viewBox="0 0 18 18"><path d="m7 16.9998189v-2.0003623h4v2.0003623h2v-3.0005434h-8v3.0005434zm-3-10.00181122h-1.52632364c-.27614237 0-.5-.22389817-.5-.50009056 0-.13995446.05863589-.27350497.16166338-.36820841l1.23156713-1.13206327h-2.36690687v12.00217346h3v-2.0003623h-3v-1.0001811h3v-1.0001811h1v-4.00072448h-1zm10 0v2.00036224h-1v4.00072448h1v1.0001811h3v1.0001811h-3v2.0003623h3v-12.00217346h-2.3695309l1.2315671 1.13206327c.2033191.186892.2166633.50325042.0298051.70660631-.0946863.10304615-.2282126.16169266-.3681417.16169266zm3-3.00054336c.5522847 0 1 .44779634 1 1.00018112v13.00235456h-18v-13.00235456c0-.55238478.44771525-1.00018112 1-1.00018112h3.45499992l4.20535144-3.86558216c.19129876-.17584288.48537447-.17584288.67667324 0l4.2053514 3.86558216zm-4 3.00054336h-8v1.00018112h8zm-2 6.00108672h1v-4.00072448h-1zm-1 0v-4.00072448h-2v4.00072448zm-3 0v-4.00072448h-1v4.00072448zm8-4.00072448c.5522847 0 1 .44779634 1 1.00018112v2.00036226h-2v-2.00036226c0-.55238478.4477153-1.00018112 1-1.00018112zm-12 0c.55228475 0 1 .44779634 1 1.00018112v2.00036226h-2v-2.00036226c0-.55238478.44771525-1.00018112 1-1.00018112zm5.99868798-7.81907007-5.24205601 4.81852671h10.48411203zm.00131202 3.81834559c-.55228475 0-1-.44779634-1-1.00018112s.44771525-1.00018112 1-1.00018112 1 .44779634 1 1.00018112-.44771525 1.00018112-1 1.00018112zm-1 11.00199236v1.0001811h2v-1.0001811z" fill-rule="evenodd"/></symbol><symbol id="icon-location" viewBox="0 0 18 18"><path d="m9.39521328 16.2688008c.79596342-.7770119 1.59208152-1.6299956 2.33285652-2.5295081 1.4020032-1.7024324 2.4323601-3.3624519 2.9354918-4.871847.2228715-.66861448.3364384-1.29323246.3364384-1.8674457 0-3.3137085-2.6862915-6-6-6-3.36356866 0-6 2.60156856-6 6 0 .57421324.11356691 1.19883122.3364384 1.8674457.50313169 1.5093951 1.53348863 3.1694146 2.93549184 4.871847.74077492.8995125 1.53689309 1.7524962 2.33285648 2.5295081.13694479.1336842.26895677.2602648.39521328.3793207.12625651-.1190559.25826849-.2456365.39521328-.3793207zm-.39521328 1.7311992s-7-6-7-11c0-4 3.13400675-7 7-7 3.8659932 0 7 3.13400675 7 7 0 5-7 11-7 11zm0-8c-1.65685425 0-3-1.34314575-3-3s1.34314575-3 3-3c1.6568542 0 3 1.34314575 3 3s-1.3431458 3-3 3zm0-1c1.1045695 0 2-.8954305 2-2s-.8954305-2-2-2-2 .8954305-2 2 .8954305 2 2 2z" fill-rule="evenodd"/></symbol><symbol id="icon-minus" viewBox="0 0 16 16"><path d="m2.00087166 7h11.99825664c.5527662 0 1.0008717.44386482 1.0008717 1 0 .55228475-.4446309 1-1.0008717 1h-11.99825664c-.55276616 0-1.00087166-.44386482-1.00087166-1 0-.55228475.44463086-1 1.00087166-1z" fill-rule="evenodd"/></symbol><symbol id="icon-newsletter" viewBox="0 0 18 18"><path d="m9 11.8482489 2-1.1428571v-1.7053918h-4v1.7053918zm-3-1.7142857v-2.1339632h6v2.1339632l3-1.71428574v-6.41967746h-12v6.41967746zm10-5.3839632 1.5299989.95624934c.2923814.18273835.4700011.50320827.4700011.8479983v8.44575236c0 1.1045695-.8954305 2-2 2h-14c-1.1045695 0-2-.8954305-2-2v-8.44575236c0-.34479003.1776197-.66525995.47000106-.8479983l1.52999894-.95624934v-2.75c0-.55228475.44771525-1 1-1h12c.5522847 0 1 .44771525 1 1zm0 1.17924764v3.07075236l-7 4-7-4v-3.07075236l-1 .625v8.44575236c0 .5522847.44771525 1 1 1h14c.5522847 0 1-.4477153 1-1v-8.44575236zm-10-1.92924764h6v1h-6zm-1 2h8v1h-8z" fill-rule="evenodd"/></symbol><symbol id="icon-orcid" viewBox="0 0 18 18"><path d="m9 1c4.418278 0 8 3.581722 8 8s-3.581722 8-8 8-8-3.581722-8-8 3.581722-8 8-8zm-2.90107518 5.2732337h-1.41865256v7.1712107h1.41865256zm4.55867178.02508949h-2.99247027v7.14612121h2.91062487c.7673039 0 1.4476365-.1483432 2.0410182-.445034s1.0511995-.7152915 1.3734671-1.2558144c.3222677-.540523.4833991-1.1603247.4833991-1.85942385 0-.68545815-.1602789-1.30270225-.4808414-1.85175082-.3205625-.54904856-.7707074-.97532211-1.3504481-1.27883343-.5797408-.30351132-1.2413173-.45526471-1.9847495-.45526471zm-.1892674 1.07933542c.7877654 0 1.4143875.22336734 1.8798852.67010873.4654977.44674138.698243 1.05546001.698243 1.82617415 0 .74343221-.2310402 1.34447791-.6931277 1.80315511-.4620874.4586773-1.0750688.6880124-1.8389625.6880124h-1.46810075v-4.98745039zm-5.08652545-3.71099194c-.21825533 0-.410525.08444276-.57681478.25333081-.16628977.16888806-.24943341.36245684-.24943341.58071218 0 .22345188.08314364.41961891.24943341.58850696.16628978.16888806.35855945.25333082.57681478.25333082.233845 0 .43390938-.08314364.60019916-.24943342.16628978-.16628977.24943342-.36375592.24943342-.59240436 0-.233845-.08314364-.43131115-.24943342-.59240437s-.36635416-.24163862-.60019916-.24163862z" fill-rule="evenodd"/></symbol><symbol id="icon-plus" viewBox="0 0 16 16"><path d="m2.00087166 7h4.99912834v-4.99912834c0-.55276616.44386482-1.00087166 1-1.00087166.55228475 0 1 .44463086 1 1.00087166v4.99912834h4.9991283c.5527662 0 1.0008717.44386482 1.0008717 1 0 .55228475-.4446309 1-1.0008717 1h-4.9991283v4.9991283c0 .5527662-.44386482 1.0008717-1 1.0008717-.55228475 0-1-.4446309-1-1.0008717v-4.9991283h-4.99912834c-.55276616 0-1.00087166-.44386482-1.00087166-1 0-.55228475.44463086-1 1.00087166-1z" fill-rule="evenodd"/></symbol><symbol id="icon-print" viewBox="0 0 18 18"><path d="m16.0049107 5h-14.00982141c-.54941618 0-.99508929.4467783-.99508929.99961498v6.00077002c0 .5570958.44271433.999615.99508929.999615h1.00491071v-3h12v3h1.0049107c.5494162 0 .9950893-.4467783.9950893-.999615v-6.00077002c0-.55709576-.4427143-.99961498-.9950893-.99961498zm-2.0049107-1v-2.00208688c0-.54777062-.4519464-.99791312-1.0085302-.99791312h-7.9829396c-.55661731 0-1.0085302.44910695-1.0085302.99791312v2.00208688zm1 10v2.0018986c0 1.103521-.9019504 1.9981014-2.0085302 1.9981014h-7.9829396c-1.1092806 0-2.0085302-.8867064-2.0085302-1.9981014v-2.0018986h-1.00491071c-1.10185739 0-1.99508929-.8874333-1.99508929-1.999615v-6.00077002c0-1.10435686.8926228-1.99961498 1.99508929-1.99961498h1.00491071v-2.00208688c0-1.10341695.90195036-1.99791312 2.0085302-1.99791312h7.9829396c1.1092806 0 2.0085302.89826062 2.0085302 1.99791312v2.00208688h1.0049107c1.1018574 0 1.9950893.88743329 1.9950893 1.99961498v6.00077002c0 1.1043569-.8926228 1.999615-1.9950893 1.999615zm-1-3h-10v5.0018986c0 .5546075.44702548.9981014 1.0085302.9981014h7.9829396c.5565964 0 1.0085302-.4491701 1.0085302-.9981014zm-9 1h8v1h-8zm0 2h5v1h-5zm9-5c-.5522847 0-1-.44771525-1-1s.4477153-1 1-1 1 .44771525 1 1-.4477153 1-1 1z" fill-rule="evenodd"/></symbol><symbol id="icon-search" viewBox="0 0 22 22"><path d="M21.697 20.261a1.028 1.028 0 01.01 1.448 1.034 1.034 0 01-1.448-.01l-4.267-4.267A9.812 9.811 0 010 9.812a9.812 9.811 0 1117.43 6.182zM9.812 18.222A8.41 8.41 0 109.81 1.403a8.41 8.41 0 000 16.82z" fill-rule="evenodd"/></symbol><symbol id="icon-social-facebook" viewBox="0 0 24 24"><path d="m6.00368507 20c-1.10660471 0-2.00368507-.8945138-2.00368507-1.9940603v-12.01187942c0-1.10128908.89451376-1.99406028 1.99406028-1.99406028h12.01187942c1.1012891 0 1.9940603.89451376 1.9940603 1.99406028v12.01187942c0 1.1012891-.88679 1.9940603-2.0032184 1.9940603h-2.9570132v-6.1960818h2.0797387l.3114113-2.414723h-2.39115v-1.54164807c0-.69911803.1941355-1.1755439 1.1966615-1.1755439l1.2786739-.00055875v-2.15974763l-.2339477-.02492088c-.3441234-.03134957-.9500153-.07025255-1.6293054-.07025255-1.8435726 0-3.1057323 1.12531866-3.1057323 3.19187953v1.78079225h-2.0850778v2.414723h2.0850778v6.1960818z" fill-rule="evenodd"/></symbol><symbol id="icon-social-twitter" viewBox="0 0 24 24"><path d="m18.8767135 6.87445248c.7638174-.46908424 1.351611-1.21167363 1.6250764-2.09636345-.7135248.43394112-1.50406.74870123-2.3464594.91677702-.6695189-.73342162-1.6297913-1.19486605-2.6922204-1.19486605-2.0399895 0-3.6933555 1.69603749-3.6933555 3.78628909 0 .29642457.0314329.58673729.0942985.8617704-3.06469922-.15890802-5.78835241-1.66547825-7.60988389-3.9574208-.3174714.56076194-.49978171 1.21167363-.49978171 1.90536824 0 1.31404706.65223085 2.47224203 1.64236444 3.15218497-.60350999-.0198635-1.17401554-.1925232-1.67222562-.47366811v.04583885c0 1.83355406 1.27302891 3.36609966 2.96411421 3.71294696-.31118484.0886217-.63651445.1329326-.97441718.1329326-.2357461 0-.47149219-.0229194-.69466516-.0672303.47149219 1.5065703 1.83253297 2.6036468 3.44975116 2.632678-1.2651707 1.0160946-2.85724264 1.6196394-4.5891906 1.6196394-.29861172 0-.59093688-.0152796-.88011875-.0504227 1.63450624 1.0726291 3.57548241 1.6990934 5.66104951 1.6990934 6.79263079 0 10.50641749-5.7711113 10.50641749-10.7751859l-.0094298-.48894775c.7229547-.53478659 1.3516109-1.20250585 1.8419628-1.96190282-.6632323.30100846-1.3751855.50422736-2.1217148.59590507z" fill-rule="evenodd"/></symbol><symbol id="icon-social-youtube" viewBox="0 0 24 24"><path d="m10.1415 14.3973208-.0005625-5.19318431 4.863375 2.60554491zm9.963-7.92753362c-.6845625-.73643756-1.4518125-.73990314-1.803375-.7826454-2.518875-.18714178-6.2971875-.18714178-6.2971875-.18714178-.007875 0-3.7861875 0-6.3050625.18714178-.352125.04274226-1.1188125.04620784-1.8039375.7826454-.5394375.56084773-.7149375 1.8344515-.7149375 1.8344515s-.18 1.49597903-.18 2.99138042v1.4024082c0 1.495979.18 2.9913804.18 2.9913804s.1755 1.2736038.7149375 1.8344515c.685125.7364376 1.5845625.7133337 1.9850625.7901542 1.44.1420891 6.12.1859866 6.12.1859866s3.78225-.005776 6.301125-.1929178c.3515625-.0433198 1.1188125-.0467854 1.803375-.783223.5394375-.5608477.7155-1.8344515.7155-1.8344515s.18-1.4954014.18-2.9913804v-1.4024082c0-1.49540139-.18-2.99138042-.18-2.99138042s-.1760625-1.27360377-.7155-1.8344515z" fill-rule="evenodd"/></symbol><symbol id="icon-subject-medicine" viewBox="0 0 18 18"><path d="m12.5 8h-6.5c-1.65685425 0-3 1.34314575-3 3v1c0 1.6568542 1.34314575 3 3 3h1v-2h-.5c-.82842712 0-1.5-.6715729-1.5-1.5s.67157288-1.5 1.5-1.5h1.5 2 1 2c1.6568542 0 3-1.34314575 3-3v-1c0-1.65685425-1.3431458-3-3-3h-2v2h1.5c.8284271 0 1.5.67157288 1.5 1.5s-.6715729 1.5-1.5 1.5zm-5.5-1v-1h-3.5c-1.38071187 0-2.5-1.11928813-2.5-2.5s1.11928813-2.5 2.5-2.5h1.02786405c.46573528 0 .92507448.10843528 1.34164078.31671843l1.13382424.56691212c.06026365-1.05041141.93116291-1.88363055 1.99667093-1.88363055 1.1045695 0 2 .8954305 2 2h2c2.209139 0 4 1.790861 4 4v1c0 2.209139-1.790861 4-4 4h-2v1h2c1.1045695 0 2 .8954305 2 2s-.8954305 2-2 2h-2c0 1.1045695-.8954305 2-2 2s-2-.8954305-2-2h-1c-2.209139 0-4-1.790861-4-4v-1c0-2.209139 1.790861-4 4-4zm0-2v-2.05652691c-.14564246-.03538148-.28733393-.08714006-.42229124-.15461871l-1.15541752-.57770876c-.27771087-.13885544-.583937-.21114562-.89442719-.21114562h-1.02786405c-.82842712 0-1.5.67157288-1.5 1.5s.67157288 1.5 1.5 1.5zm4 1v1h1.5c.2761424 0 .5-.22385763.5-.5s-.2238576-.5-.5-.5zm-1 1v-5c0-.55228475-.44771525-1-1-1s-1 .44771525-1 1v5zm-2 4v5c0 .5522847.44771525 1 1 1s1-.4477153 1-1v-5zm3 2v2h2c.5522847 0 1-.4477153 1-1s-.4477153-1-1-1zm-4-1v-1h-.5c-.27614237 0-.5.2238576-.5.5s.22385763.5.5.5zm-3.5-9h1c.27614237 0 .5.22385763.5.5s-.22385763.5-.5.5h-1c-.27614237 0-.5-.22385763-.5-.5s.22385763-.5.5-.5z" fill-rule="evenodd"/></symbol><symbol id="icon-success" viewBox="0 0 18 18"><path d="m9 0c4.9705627 0 9 4.02943725 9 9 0 4.9705627-4.0294373 9-9 9-4.97056275 0-9-4.0294373-9-9 0-4.97056275 4.02943725-9 9-9zm3.4860198 4.98163161-4.71802968 5.50657859-2.62834168-2.02300024c-.42862421-.36730544-1.06564993-.30775346-1.42283677.13301307-.35718685.44076653-.29927542 1.0958383.12934879 1.46314377l3.40735508 2.7323063c.42215801.3385221 1.03700951.2798252 1.38749189-.1324571l5.38450527-6.33394549c.3613513-.43716226.3096573-1.09278382-.115462-1.46437175-.4251192-.37158792-1.0626796-.31842941-1.4240309.11873285z" fill-rule="evenodd"/></symbol><symbol id="icon-table" viewBox="0 0 18 18"><path d="m16.0049107 2c1.1018574 0 1.9950893.89706013 1.9950893 2.00585866v9.98828264c0 1.1078052-.8926228 2.0058587-1.9950893 2.0058587l-4.0059107-.001.001.001h-1l-.001-.001h-5l.001.001h-1l-.001-.001-3.00391071.001c-1.10185739 0-1.99508929-.8970601-1.99508929-2.0058587v-9.98828264c0-1.10780515.8926228-2.00585866 1.99508929-2.00585866zm-11.0059107 5h-3.999v6.9941413c0 .5572961.44630695 1.0058587.99508929 1.0058587h3.00391071zm6 0h-5v8h5zm5.0059107-4h-4.0059107v3h5.001v1h-5.001v7.999l4.0059107.001c.5487152 0 .9950893-.4488783.9950893-1.0058587v-9.98828264c0-.55729607-.446307-1.00585866-.9950893-1.00585866zm-12.5049107 9c.27614237 0 .5.2238576.5.5s-.22385763.5-.5.5h-1c-.27614237 0-.5-.2238576-.5-.5s.22385763-.5.5-.5zm12 0c.2761424 0 .5.2238576.5.5s-.2238576.5-.5.5h-2c-.2761424 0-.5-.2238576-.5-.5s.2238576-.5.5-.5zm-6 0c.27614237 0 .5.2238576.5.5s-.22385763.5-.5.5h-2c-.27614237 0-.5-.2238576-.5-.5s.22385763-.5.5-.5zm-6-2c.27614237 0 .5.2238576.5.5s-.22385763.5-.5.5h-1c-.27614237 0-.5-.2238576-.5-.5s.22385763-.5.5-.5zm12 0c.2761424 0 .5.2238576.5.5s-.2238576.5-.5.5h-2c-.2761424 0-.5-.2238576-.5-.5s.2238576-.5.5-.5zm-6 0c.27614237 0 .5.2238576.5.5s-.22385763.5-.5.5h-2c-.27614237 0-.5-.2238576-.5-.5s.22385763-.5.5-.5zm-6-2c.27614237 0 .5.22385763.5.5s-.22385763.5-.5.5h-1c-.27614237 0-.5-.22385763-.5-.5s.22385763-.5.5-.5zm12 0c.2761424 0 .5.22385763.5.5s-.2238576.5-.5.5h-2c-.2761424 0-.5-.22385763-.5-.5s.2238576-.5.5-.5zm-6 0c.27614237 0 .5.22385763.5.5s-.22385763.5-.5.5h-2c-.27614237 0-.5-.22385763-.5-.5s.22385763-.5.5-.5zm1.499-5h-5v3h5zm-6 0h-3.00391071c-.54871518 0-.99508929.44887827-.99508929 1.00585866v1.99414134h3.999z" fill-rule="evenodd"/></symbol><symbol id="icon-tick-circle" viewBox="0 0 24 24"><path d="m12 2c5.5228475 0 10 4.4771525 10 10s-4.4771525 10-10 10-10-4.4771525-10-10 4.4771525-10 10-10zm0 1c-4.97056275 0-9 4.02943725-9 9 0 4.9705627 4.02943725 9 9 9 4.9705627 0 9-4.0294373 9-9 0-4.97056275-4.0294373-9-9-9zm4.2199868 5.36606669c.3613514-.43716226.9989118-.49032077 1.424031-.11873285s.4768133 1.02720949.115462 1.46437175l-6.093335 6.94397871c-.3622945.4128716-.9897871.4562317-1.4054264.0971157l-3.89719065-3.3672071c-.42862421-.3673054-.48653564-1.0223772-.1293488-1.4631437s.99421256-.5003185 1.42283677-.1330131l3.11097438 2.6987741z" fill-rule="evenodd"/></symbol><symbol id="icon-tick" viewBox="0 0 16 16"><path d="m6.76799012 9.21106946-3.1109744-2.58349728c-.42862421-.35161617-1.06564993-.29460792-1.42283677.12733148s-.29927541 1.04903009.1293488 1.40064626l3.91576307 3.23873978c.41034319.3393961 1.01467563.2976897 1.37450571-.0948578l6.10568327-6.660841c.3613513-.41848908.3096572-1.04610608-.115462-1.4018218-.4251192-.35571573-1.0626796-.30482786-1.424031.11366122z" fill-rule="evenodd"/></symbol><symbol id="icon-update" viewBox="0 0 18 18"><path d="m1 13v1c0 .5522847.44771525 1 1 1h14c.5522847 0 1-.4477153 1-1v-1h-1v-10h-14v10zm16-1h1v2c0 1.1045695-.8954305 2-2 2h-14c-1.1045695 0-2-.8954305-2-2v-2h1v-9c0-.55228475.44771525-1 1-1h14c.5522847 0 1 .44771525 1 1zm-1 0v1h-4.5857864l-1 1h-2.82842716l-1-1h-4.58578644v-1h5l1 1h2l1-1zm-13-8h12v7h-12zm1 1v5h10v-5zm1 1h4v1h-4zm0 2h4v1h-4z" fill-rule="evenodd"/></symbol><symbol id="icon-upload" viewBox="0 0 18 18"><path d="m10.0046024 0c.5497429 0 1.3179837.32258606 1.707238.71184039l4.5763192 4.57631922c.3931386.39313859.7118404 1.16760135.7118404 1.71431368v8.98899651c0 1.1092806-.8945138 2.0085302-1.9940603 2.0085302h-12.01187942c-1.10128908 0-1.99406028-.8926228-1.99406028-1.9950893v-14.00982141c0-1.10185739.88743329-1.99508929 1.99961498-1.99508929zm0 1h-7.00498742c-.55709576 0-.99961498.44271433-.99961498.99508929v14.00982141c0 .5500396.44491393.9950893.99406028.9950893h12.01187942c.5463747 0 .9940603-.4506622.9940603-1.0085302v-8.98899651c0-.28393444-.2150684-.80332809-.4189472-1.0072069l-4.5763192-4.57631922c-.2038461-.20384606-.718603-.41894717-1.0001312-.41894717zm-1.85576936 4.14572769c.19483374-.19483375.51177826-.19377714.70556874.00001334l2.59099082 2.59099079c.1948411.19484112.1904373.51514474.0027906.70279143-.1932998.19329987-.5046517.19237083-.7001856-.00692852l-1.74638687-1.7800176v6.14827687c0 .2717771-.23193359.492096-.5.492096-.27614237 0-.5-.216372-.5-.492096v-6.14827641l-1.74627892 1.77990922c-.1933927.1971171-.51252214.19455839-.70016883.0069117-.19329987-.19329988-.19100584-.50899493.00277731-.70277808z" fill-rule="evenodd"/></symbol><symbol id="icon-video" viewBox="0 0 18 18"><path d="m16.0049107 2c1.1018574 0 1.9950893.89706013 1.9950893 2.00585866v9.98828264c0 1.1078052-.8926228 2.0058587-1.9950893 2.0058587h-14.00982141c-1.10185739 0-1.99508929-.8970601-1.99508929-2.0058587v-9.98828264c0-1.10780515.8926228-2.00585866 1.99508929-2.00585866zm0 1h-14.00982141c-.54871518 0-.99508929.44887827-.99508929 1.00585866v9.98828264c0 .5572961.44630695 1.0058587.99508929 1.0058587h14.00982141c.5487152 0 .9950893-.4488783.9950893-1.0058587v-9.98828264c0-.55729607-.446307-1.00585866-.9950893-1.00585866zm-8.30912922 2.24944486 4.60460462 2.73982242c.9365543.55726659.9290753 1.46522435 0 2.01804082l-4.60460462 2.7398224c-.93655425.5572666-1.69578148.1645632-1.69578148-.8937585v-5.71016863c0-1.05087579.76670616-1.446575 1.69578148-.89375851zm-.67492769.96085624v5.5750128c0 .2995102-.10753745.2442517.16578928.0847713l4.58452283-2.67497259c.3050619-.17799716.3051624-.21655446 0-.39461026l-4.58452283-2.67497264c-.26630747-.15538481-.16578928-.20699944-.16578928.08477139z" fill-rule="evenodd"/></symbol><symbol id="icon-warning" viewBox="0 0 18 18"><path d="m9 11.75c.69035594 0 1.25.5596441 1.25 1.25s-.55964406 1.25-1.25 1.25-1.25-.5596441-1.25-1.25.55964406-1.25 1.25-1.25zm.41320045-7.75c.55228475 0 1.00000005.44771525 1.00000005 1l-.0034543.08304548-.3333333 4c-.043191.51829212-.47645714.91695452-.99654578.91695452h-.15973424c-.52008864 0-.95335475-.3986624-.99654576-.91695452l-.33333333-4c-.04586475-.55037702.36312325-1.03372649.91350028-1.07959124l.04148683-.00259031zm-.41320045 14c-4.97056275 0-9-4.0294373-9-9 0-4.97056275 4.02943725-9 9-9 4.9705627 0 9 4.02943725 9 9 0 4.9705627-4.0294373 9-9 9z" fill-rule="evenodd"/></symbol><symbol id="icon-checklist-banner" viewBox="0 0 56.69 56.69"><path style="fill:none" d="M0 0h56.69v56.69H0z"/><clipPath id="b"><use xlink:href="#a" style="overflow:visible"/></clipPath><path d="M21.14 34.46c0-6.77 5.48-12.26 12.24-12.26s12.24 5.49 12.24 12.26-5.48 12.26-12.24 12.26c-6.76-.01-12.24-5.49-12.24-12.26zm19.33 10.66 10.23 9.22s1.21 1.09 2.3-.12l2.09-2.32s1.09-1.21-.12-2.3l-10.23-9.22m-19.29-5.92c0-4.38 3.55-7.94 7.93-7.94s7.93 3.55 7.93 7.94c0 4.38-3.55 7.94-7.93 7.94-4.38-.01-7.93-3.56-7.93-7.94zm17.58 12.99 4.14-4.81" style="clip-path:url(#b);fill:none;stroke:#01324b;stroke-width:2;stroke-linecap:round"/><path d="M8.26 9.75H28.6M8.26 15.98H28.6m-20.34 6.2h12.5m14.42-5.2V4.86s0-2.93-2.93-2.93H4.13s-2.93 0-2.93 2.93v37.57s0 2.93 2.93 2.93h15.01M8.26 9.75H28.6M8.26 15.98H28.6m-20.34 6.2h12.5" style="clip-path:url(#b);fill:none;stroke:#01324b;stroke-width:2;stroke-linecap:round;stroke-linejoin:round"/></symbol><symbol id="icon-chevron-down" viewBox="0 0 16 16"><path d="m5.58578644 3-3.29289322-3.29289322c-.39052429-.39052429-.39052429-1.02368927 0-1.41421356s1.02368927-.39052429 1.41421356 0l4 4c.39052429.39052429.39052429 1.02368927 0 1.41421356l-4 4c-.39052429.39052429-1.02368927.39052429-1.41421356 0s-.39052429-1.02368927 0-1.41421356z" fill-rule="evenodd" transform="matrix(0 1 -1 0 11 1)"/></symbol><symbol id="icon-eds-i-arrow-right-medium" viewBox="0 0 24 24"><path d="m12.728 3.293 7.98 7.99a.996.996 0 0 1 .281.561l.011.157c0 .32-.15.605-.384.788l-7.908 7.918a1 1 0 0 1-1.416-1.414L17.576 13H4a1 1 0 0 1 0-2h13.598l-6.285-6.293a1 1 0 0 1-.082-1.32l.083-.095a1 1 0 0 1 1.414.001Z"/></symbol><symbol id="icon-eds-i-chevron-down-medium" viewBox="0 0 16 16"><path d="m2.00087166 7h4.99912834v-4.99912834c0-.55276616.44386482-1.00087166 1-1.00087166.55228475 0 1 .44463086 1 1.00087166v4.99912834h4.9991283c.5527662 0 1.0008717.44386482 1.0008717 1 0 .55228475-.4446309 1-1.0008717 1h-4.9991283v4.9991283c0 .5527662-.44386482 1.0008717-1 1.0008717-.55228475 0-1-.4446309-1-1.0008717v-4.9991283h-4.99912834c-.55276616 0-1.00087166-.44386482-1.00087166-1 0-.55228475.44463086-1 1.00087166-1z" fill-rule="evenodd"/></symbol><symbol id="icon-eds-i-chevron-down-small" viewBox="0 0 16 16"><path d="M13.692 5.278a1 1 0 0 1 .03 1.414L9.103 11.51a1.491 1.491 0 0 1-2.188.019L2.278 6.692a1 1 0 0 1 1.444-1.384L8 9.771l4.278-4.463a1 1 0 0 1 1.318-.111l.096.081Z"/></symbol><symbol id="icon-eds-i-chevron-right-medium" viewBox="0 0 10 10"><path d="m5.96738168 4.70639573 2.39518594-2.41447274c.37913917-.38219212.98637524-.38972225 1.35419292-.01894278.37750606.38054586.37784436.99719163-.00013556 1.37821513l-4.03074001 4.06319683c-.37758093.38062133-.98937525.38100976-1.367372-.00003075l-4.03091981-4.06337806c-.37759778-.38063832-.38381821-.99150444-.01600053-1.3622839.37750607-.38054587.98772445-.38240057 1.37006824.00302197l2.39538588 2.4146743.96295325.98624457z" fill-rule="evenodd" transform="matrix(0 -1 1 0 0 10)"/></symbol><symbol id="icon-eds-i-chevron-right-small" viewBox="0 0 10 10"><path d="m5.96738168 4.70639573 2.39518594-2.41447274c.37913917-.38219212.98637524-.38972225 1.35419292-.01894278.37750606.38054586.37784436.99719163-.00013556 1.37821513l-4.03074001 4.06319683c-.37758093.38062133-.98937525.38100976-1.367372-.00003075l-4.03091981-4.06337806c-.37759778-.38063832-.38381821-.99150444-.01600053-1.3622839.37750607-.38054587.98772445-.38240057 1.37006824.00302197l2.39538588 2.4146743.96295325.98624457z" fill-rule="evenodd" transform="matrix(0 -1 1 0 0 10)"/></symbol><symbol id="icon-eds-i-chevron-up-medium" viewBox="0 0 16 16"><path d="m2.00087166 7h11.99825664c.5527662 0 1.0008717.44386482 1.0008717 1 0 .55228475-.4446309 1-1.0008717 1h-11.99825664c-.55276616 0-1.00087166-.44386482-1.00087166-1 0-.55228475.44463086-1 1.00087166-1z" fill-rule="evenodd"/></symbol><symbol id="icon-eds-i-close-medium" viewBox="0 0 16 16"><path d="m2.29679575 12.2772478c-.39658757.3965876-.39438847 1.0328109-.00062148 1.4265779.39651227.3965123 1.03246768.3934888 1.42657791-.0006214l4.27724782-4.27724787 4.2772478 4.27724787c.3965876.3965875 1.0328109.3943884 1.4265779.0006214.3965123-.3965122.3934888-1.0324677-.0006214-1.4265779l-4.27724787-4.2772478 4.27724787-4.27724782c.3965875-.39658757.3943884-1.03281091.0006214-1.42657791-.3965122-.39651226-1.0324677-.39348875-1.4265779.00062148l-4.2772478 4.27724782-4.27724782-4.27724782c-.39658757-.39658757-1.03281091-.39438847-1.42657791-.00062148-.39651226.39651227-.39348875 1.03246768.00062148 1.42657791l4.27724782 4.27724782z" fill-rule="evenodd"/></symbol><symbol id="icon-eds-i-download-medium" viewBox="0 0 16 16"><path d="m12.9975267 12.999368c.5467123 0 1.0024733.4478567 1.0024733 1.000316 0 .5563109-.4488226 1.000316-1.0024733 1.000316h-9.99505341c-.54671233 0-1.00247329-.4478567-1.00247329-1.000316 0-.5563109.44882258-1.000316 1.00247329-1.000316zm-4.9975267-11.999368c.55228475 0 1 .44497754 1 .99589209v6.80214418l2.4816273-2.48241149c.3928222-.39294628 1.0219732-.4006883 1.4030652-.01947579.3911302.39125371.3914806 1.02525073-.0001404 1.41699553l-4.17620792 4.17752758c-.39120769.3913313-1.02508144.3917306-1.41671995-.0000316l-4.17639421-4.17771394c-.39122513-.39134876-.39767006-1.01940351-.01657797-1.40061601.39113012-.39125372 1.02337105-.3931606 1.41951349.00310701l2.48183446 2.48261871v-6.80214418c0-.55001601.44386482-.99589209 1-.99589209z" fill-rule="evenodd"/></symbol><symbol id="icon-eds-i-info-filled-medium" viewBox="0 0 18 18"><path d="m9 0c4.9705627 0 9 4.02943725 9 9 0 4.9705627-4.0294373 9-9 9-4.97056275 0-9-4.0294373-9-9 0-4.97056275 4.02943725-9 9-9zm0 7h-1.5l-.11662113.00672773c-.49733868.05776511-.88337887.48043643-.88337887.99327227 0 .47338693.32893365.86994729.77070917.97358929l.1126697.01968298.11662113.00672773h.5v3h-.5l-.11662113.0067277c-.42082504.0488782-.76196299.3590206-.85696816.7639815l-.01968298.1126697-.00672773.1166211.00672773.1166211c.04887817.4208251.35902055.761963.76398144.8569682l.1126697.019683.11662113.0067277h3l.1166211-.0067277c.4973387-.0577651.8833789-.4804365.8833789-.9932723 0-.4733869-.3289337-.8699473-.7707092-.9735893l-.1126697-.019683-.1166211-.0067277h-.5v-4l-.00672773-.11662113c-.04887817-.42082504-.35902055-.76196299-.76398144-.85696816l-.1126697-.01968298zm0-3.25c-.69035594 0-1.25.55964406-1.25 1.25s.55964406 1.25 1.25 1.25 1.25-.55964406 1.25-1.25-.55964406-1.25-1.25-1.25z" fill-rule="evenodd"/></symbol><symbol id="icon-eds-i-mail-medium" viewBox="0 0 24 24"><path d="m19.462 0c1.413 0 2.538 1.184 2.538 2.619v12.762c0 1.435-1.125 2.619-2.538 2.619h-16.924c-1.413 0-2.538-1.184-2.538-2.619v-12.762c0-1.435 1.125-2.619 2.538-2.619zm.538 5.158-7.378 6.258a2.549 2.549 0 0 1 -3.253-.008l-7.369-6.248v10.222c0 .353.253.619.538.619h16.924c.285 0 .538-.266.538-.619zm-.538-3.158h-16.924c-.264 0-.5.228-.534.542l8.65 7.334c.2.165.492.165.684.007l8.656-7.342-.001-.025c-.044-.3-.274-.516-.531-.516z"/></symbol><symbol id="icon-eds-i-menu-medium" viewBox="0 0 24 24"><path d="M21 4a1 1 0 0 1 0 2H3a1 1 0 1 1 0-2h18Zm-4 7a1 1 0 0 1 0 2H3a1 1 0 0 1 0-2h14Zm4 7a1 1 0 0 1 0 2H3a1 1 0 0 1 0-2h18Z"/></symbol><symbol id="icon-eds-i-search-medium" viewBox="0 0 24 24"><path d="M11 1c5.523 0 10 4.477 10 10 0 2.4-.846 4.604-2.256 6.328l3.963 3.965a1 1 0 0 1-1.414 1.414l-3.965-3.963A9.959 9.959 0 0 1 11 21C5.477 21 1 16.523 1 11S5.477 1 11 1Zm0 2a8 8 0 1 0 0 16 8 8 0 0 0 0-16Z"/></symbol><symbol id="icon-eds-i-user-single-medium" viewBox="0 0 24 24"><path d="M12 1a5 5 0 1 1 0 10 5 5 0 0 1 0-10Zm0 2a3 3 0 1 0 0 6 3 3 0 0 0 0-6Zm-.406 9.008a8.965 8.965 0 0 1 6.596 2.494A9.161 9.161 0 0 1 21 21.025V22a1 1 0 0 1-1 1H4a1 1 0 0 1-1-1v-.985c.05-4.825 3.815-8.777 8.594-9.007Zm.39 1.992-.299.006c-3.63.175-6.518 3.127-6.678 6.775L5 21h13.998l-.009-.268a7.157 7.157 0 0 0-1.97-4.573l-.214-.213A6.967 6.967 0 0 0 11.984 14Z"/></symbol><symbol id="icon-eds-i-warning-filled-medium" viewBox="0 0 18 18"><path d="m9 11.75c.69035594 0 1.25.5596441 1.25 1.25s-.55964406 1.25-1.25 1.25-1.25-.5596441-1.25-1.25.55964406-1.25 1.25-1.25zm.41320045-7.75c.55228475 0 1.00000005.44771525 1.00000005 1l-.0034543.08304548-.3333333 4c-.043191.51829212-.47645714.91695452-.99654578.91695452h-.15973424c-.52008864 0-.95335475-.3986624-.99654576-.91695452l-.33333333-4c-.04586475-.55037702.36312325-1.03372649.91350028-1.07959124l.04148683-.00259031zm-.41320045 14c-4.97056275 0-9-4.0294373-9-9 0-4.97056275 4.02943725-9 9-9 4.9705627 0 9 4.02943725 9 9 0 4.9705627-4.0294373 9-9 9z" fill-rule="evenodd"/></symbol><symbol id="icon-expand-image" viewBox="0 0 18 18"><path d="m7.49754099 11.9178212c.38955542-.3895554.38761957-1.0207846-.00290473-1.4113089-.39324695-.3932469-1.02238878-.3918247-1.41130883-.0029047l-4.10273549 4.1027355.00055454-3.5103985c.00008852-.5603185-.44832171-1.006032-1.00155062-1.0059446-.53903074.0000852-.97857527.4487442-.97866268 1.0021075l-.00093318 5.9072465c-.00008751.553948.44841131 1.001882 1.00174994 1.0017946l5.906983-.0009331c.5539233-.0000875 1.00197907-.4486389 1.00206646-1.0018679.00008515-.5390307-.45026621-.9784332-1.00588841-.9783454l-3.51010549.0005545zm3.00571741-5.83449376c-.3895554.38955541-.3876196 1.02078454.0029047 1.41130883.393247.39324696 1.0223888.39182478 1.4113089.00290473l4.1027355-4.10273549-.0005546 3.5103985c-.0000885.56031852.4483217 1.006032 1.0015506 1.00594461.5390308-.00008516.9785753-.44874418.9786627-1.00210749l.0009332-5.9072465c.0000875-.553948-.4484113-1.00188204-1.0017499-1.00179463l-5.906983.00093313c-.5539233.00008751-1.0019791.44863892-1.0020665 1.00186784-.0000852.53903074.4502662.97843325 1.0058884.97834547l3.5101055-.00055449z" fill-rule="evenodd"/></symbol><symbol id="icon-github" viewBox="0 0 100 100"><path fill-rule="evenodd" clip-rule="evenodd" d="M48.854 0C21.839 0 0 22 0 49.217c0 21.756 13.993 40.172 33.405 46.69 2.427.49 3.316-1.059 3.316-2.362 0-1.141-.08-5.052-.08-9.127-13.59 2.934-16.42-5.867-16.42-5.867-2.184-5.704-5.42-7.17-5.42-7.17-4.448-3.015.324-3.015.324-3.015 4.934.326 7.523 5.052 7.523 5.052 4.367 7.496 11.404 5.378 14.235 4.074.404-3.178 1.699-5.378 3.074-6.6-10.839-1.141-22.243-5.378-22.243-24.283 0-5.378 1.94-9.778 5.014-13.2-.485-1.222-2.184-6.275.486-13.038 0 0 4.125-1.304 13.426 5.052a46.97 46.97 0 0 1 12.214-1.63c4.125 0 8.33.571 12.213 1.63 9.302-6.356 13.427-5.052 13.427-5.052 2.67 6.763.97 11.816.485 13.038 3.155 3.422 5.015 7.822 5.015 13.2 0 18.905-11.404 23.06-22.324 24.283 1.78 1.548 3.316 4.481 3.316 9.126 0 6.6-.08 11.897-.08 13.526 0 1.304.89 2.853 3.316 2.364 19.412-6.52 33.405-24.935 33.405-46.691C97.707 22 75.788 0 48.854 0z"/></symbol><symbol id="icon-springer-arrow-left"><path d="M15 7a1 1 0 000-2H3.385l2.482-2.482a.994.994 0 00.02-1.403 1.001 1.001 0 00-1.417 0L.294 5.292a1.001 1.001 0 000 1.416l4.176 4.177a.991.991 0 001.4.016 1 1 0 00-.003-1.42L3.385 7H15z"/></symbol><symbol id="icon-springer-arrow-right"><path d="M1 7a1 1 0 010-2h11.615l-2.482-2.482a.994.994 0 01-.02-1.403 1.001 1.001 0 011.417 0l4.176 4.177a1.001 1.001 0 010 1.416l-4.176 4.177a.991.991 0 01-1.4.016 1 1 0 01.003-1.42L12.615 7H1z"/></symbol><symbol id="icon-submit-open" viewBox="0 0 16 17"><path d="M12 0c1.10457 0 2 .895431 2 2v5c0 .276142-.223858.5-.5.5S13 7.276142 13 7V2c0-.512836-.38604-.935507-.883379-.993272L12 1H6v3c0 1.10457-.89543 2-2 2H1v8c0 .512836.38604.935507.883379.993272L2 15h6.5c.276142 0 .5.223858.5.5s-.223858.5-.5.5H2c-1.104569 0-2-.89543-2-2V5.828427c0-.530433.210714-1.039141.585786-1.414213L4.414214.585786C4.789286.210714 5.297994 0 5.828427 0H12Zm3.41 11.14c.250899.250899.250274.659726 0 .91-.242954.242954-.649606.245216-.9-.01l-1.863671-1.900337.001043 5.869492c0 .356992-.289839.637138-.647372.637138-.347077 0-.647371-.285256-.647371-.637138l-.001043-5.869492L9.5 12.04c-.253166.258042-.649726.260274-.9.01-.242954-.242954-.252269-.657731 0-.91l2.942184-2.951303c.250908-.250909.66127-.252277.91353-.000017L15.41 11.14ZM5 1.413 1.413 5H4c.552285 0 1-.447715 1-1V1.413ZM11 3c.276142 0 .5.223858.5.5s-.223858.5-.5.5H7.5c-.276142 0-.5-.223858-.5-.5s.223858-.5.5-.5H11Zm0 2c.276142 0 .5.223858.5.5s-.223858.5-.5.5H7.5c-.276142 0-.5-.223858-.5-.5s.223858-.5.5-.5H11Z" fill-rule="nonzero"/></symbol></svg> </div> </footer> <div class="c-site-messages message u-hide u-hide-print c-site-messages--nature-briefing c-site-messages--nature-briefing-email-variant c-site-messages--nature-briefing-redesign-2020 sans-serif c-site-messages--nature-briefing-transres" data-component-id="nature-briefing-banner" data-component-expirydays="30" data-component-trigger-scroll-percentage="15" data-track="in-view" data-track-action="in-view" data-track-category="nature briefing" data-track-label="Briefing banner visible: TranslationalResearch"> <div class="c-site-messages__banner-large"> <div class="c-site-messages__close-container"> <button class="c-site-messages__close" data-track="click" data-track-category="nature briefing" data-track-label="Briefing banner dismiss: TranslationalResearch"> <svg width="25px" height="25px" focusable="false" aria-hidden="true" viewBox="0 0 25 25" version="1.1" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"> <title>Close banner</title> <defs></defs> <g stroke="none" stroke-width="1" fill="none" fill-rule="evenodd"> <rect opacity="0" x="0" y="0" width="25" height="25"></rect> <path d="M6.29679575,16.2772478 C5.90020818,16.6738354 5.90240728,17.3100587 6.29617427,17.7038257 C6.69268654,18.100338 7.32864195,18.0973145 7.72275218,17.7032043 L12,13.4259564 L16.2772478,17.7032043 C16.6738354,18.0997918 17.3100587,18.0975927 17.7038257,17.7038257 C18.100338,17.3073135 18.0973145,16.671358 17.7032043,16.2772478 L13.4259564,12 L17.7032043,7.72275218 C18.0997918,7.32616461 18.0975927,6.68994127 17.7038257,6.29617427 C17.3073135,5.89966201 16.671358,5.90268552 16.2772478,6.29679575 L12,10.5740436 L7.72275218,6.29679575 C7.32616461,5.90020818 6.68994127,5.90240728 6.29617427,6.29617427 C5.89966201,6.69268654 5.90268552,7.32864195 6.29679575,7.72275218 L10.5740436,12 L6.29679575,16.2772478 Z" fill="#ffffff"></path> </g> </svg> <span class="visually-hidden">Close</span> </button> </div> <div class="c-site-messages__form-container"> <div class="grid grid-12 last"> <div class="grid grid-4"> <img alt="Nature Briefing: Translational Research" src="/static/images/logos/nature-briefing-logo-transres-white-1245a3c374.svg" width="213" height="40"> <p class="c-site-messages--nature-briefing__strapline extra-tight-line-height">Sign up for the <em>Nature Briefing: Translational Research</em> newsletter — top stories in biotechnology, drug discovery and pharma.</p> </div> <div class="grid grid-8 last"> <form action="https://www.nature.com/briefing/translational_research" method="post" data-location="banner" data-track="signup_nature_briefing_banner" data-track-action="transmit-form" data-track-category="nature briefing" data-track-label="Briefing banner submit: TranslationalResearch"> <input id="briefing-banner-signup-form-input-track-originReferralPoint" type="hidden" name="track_originReferralPoint" value="TransResBriefingBanner"> <input id="briefing-banner-signup-form-input-track-formType" type="hidden" name="track_formType" value="DirectEmailBanner"> <input type="hidden" value="false" name="gdpr_tick" id="gdpr_tick_banner"> <input type="hidden" value="false" name="marketing" id="marketing_input_banner"> <input type="hidden" value="false" name="marketing_tick" id="marketing_tick_banner"> <input type="hidden" value="TransResBriefingBanner" name="brieferEntryPoint" id="brieferEntryPoint_banner"> <label class="nature-briefing-banner__email-label" for="emailAddress">Email address</label> <div class="nature-briefing-banner__email-wrapper"> <input class="nature-briefing-banner__email-input box-sizing text14" type="email" id="emailAddress" name="emailAddress" value="" placeholder="e.g. jo.smith@university.ac.uk" required data-test-element="briefing-emailbanner-email-input"> <input type="hidden" value="true" name="N:translational_research" id="defaultNewsletter_banner"> <button type="submit" class="nature-briefing-banner__submit-button box-sizing text14" data-test-element="briefing-emailbanner-signup-button">Sign up</button> </div> <div class="nature-briefing-banner__checkbox-wrapper grid grid-12 last"> <input class="nature-briefing-banner__checkbox-checkbox" id="gdpr-briefing-banner-checkbox" type="checkbox" name="gdpr" value="true" data-test-element="briefing-emailbanner-gdpr-checkbox" required> <label class="nature-briefing-banner__checkbox-label box-sizing text13 sans-serif block tighten-line-height" for="gdpr-briefing-banner-checkbox">I agree my information will be processed in accordance with the <em>Nature</em> and Springer Nature Limited <a href="https://www.nature.com/info/privacy">Privacy Policy</a>.</label> </div> </form> </div> </div> </div> </div> <div class="c-site-messages__banner-small"> <div class="c-site-messages__close-container"> <button class="c-site-messages__close" data-track="click" data-track-category="nature briefing" data-track-label="Briefing banner dismiss: TranslationalResearch"> <svg width="25px" height="25px" focusable="false" aria-hidden="true" viewBox="0 0 25 25" version="1.1" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"> <title>Close banner</title> <defs></defs> <g stroke="none" stroke-width="1" fill="none" fill-rule="evenodd"> <rect opacity="0" x="0" y="0" width="25" height="25"></rect> <path d="M6.29679575,16.2772478 C5.90020818,16.6738354 5.90240728,17.3100587 6.29617427,17.7038257 C6.69268654,18.100338 7.32864195,18.0973145 7.72275218,17.7032043 L12,13.4259564 L16.2772478,17.7032043 C16.6738354,18.0997918 17.3100587,18.0975927 17.7038257,17.7038257 C18.100338,17.3073135 18.0973145,16.671358 17.7032043,16.2772478 L13.4259564,12 L17.7032043,7.72275218 C18.0997918,7.32616461 18.0975927,6.68994127 17.7038257,6.29617427 C17.3073135,5.89966201 16.671358,5.90268552 16.2772478,6.29679575 L12,10.5740436 L7.72275218,6.29679575 C7.32616461,5.90020818 6.68994127,5.90240728 6.29617427,6.29617427 C5.89966201,6.69268654 5.90268552,7.32864195 6.29679575,7.72275218 L10.5740436,12 L6.29679575,16.2772478 Z" fill="#ffffff"></path> </g> </svg> <span class="visually-hidden">Close</span> </button> </div> <div class="c-site-messages__content text14"> <span class="c-site-messages--nature-briefing__strapline strong">Get what matters in translational research, free to your inbox weekly.</span> <a class="nature-briefing__link text14 sans-serif" data-track="click" data-track-category="nature briefing" data-track-label="Small-screen banner CTA to site" data-test-element="briefing-banner-link" target="_blank" rel="noreferrer noopener" href="/briefing/translational-research/?brieferEntryPoint=TransResBriefingBanner">Sign up for Nature Briefing: Translational Research </a> </div> </div> </div> <noscript> <img hidden src="https://verify.nature.com/verify/nature.png" width="0" height="0" style="display: none" alt=""> </noscript> <script src="//content.readcube.com/ping?doi=10.1038/s41587-025-02570-7&format=js&last_modified=2025-02-18" async></script> </body> </html>

CINXE.COM

Sustained in situ protein production and release in the mammalian gut by an engineered bacteriophage | Nature Biotechnology