CINXE.COM

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class="field--item"><a href="https://www.alnylam.it/">Italiano</a></div> </div> </span> </div> </div> </div> </div> </section> </div> </div> </div> </div> <div id="whole-header-top" class="container-fluid"> <div class="header-top-left col-sm-2"> <div class="region region-header-top-left"> <a class="logo navbar-btn pull-left" href="/" title="Home" rel="home"> <img src="/themes/custom/alnylam/logo.svg" alt="Home" /> </a> </div> </div> <div class="header-top-middle col-sm-9"> <div class="region region-header-top-middle"> <section id="block-alnylam-topnavigation-3" class="block block-superfish block-superfishtop-navigation clearfix"> <ul id="superfish-top-navigation" class="menu sf-menu sf-top-navigation sf-horizontal sf-style-none"> <li id="top-navigation-menu-link-content64f38306-897f-4a7c-99eb-affe953acf01" class="sf-depth-1 menuparent"><span class="sf-depth-1 menuparent nolink">Investors</span><ul><li id="top-navigation-menu-link-content0099a821-634f-457b-bfed-bba6d6235d4f" 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paragraph--view-mode--default"> <div class="language-switcher-main"> <span class="label-text"> <div class="field field--name-field-label field--type-string field--label-hidden field--item">Germany </div> </span><span class="link-text"> <div class="field field--name-field-link1 field--type-link field--label-hidden field--items"> <div class="field--item"><a href="https://www.alnylam.de/">Deutsch</a></div> </div> </span> </div> </div> </div> <div class="field--item"> <div class="paragraph paragraph--type--language-links paragraph-id--121 paragraph--view-mode--default"> <div class="language-switcher-main"> <span class="label-text"> <div class="field field--name-field-label field--type-string field--label-hidden field--item">Taiwan</div> </span><span class="link-text"> <div class="field field--name-field-link1 field--type-link field--label-hidden field--items"> <div class="field--item"><a href="/alnylam-taiwan">繁體中文</a></div> </div> </span> </div> </div> </div> <div class="field--item"> <div class="paragraph paragraph--type--language-links paragraph-id--1514 paragraph--view-mode--default"> <div class="language-switcher-main"> <span class="label-text"> <div class="field field--name-field-label field--type-string field--label-hidden field--item">Ireland </div> </span><span class="link-text"> <div class="field field--name-field-link1 field--type-link field--label-hidden field--items"> <div class="field--item"><a href="/alnylam-ireland">English</a></div> </div> </span> </div> </div> </div> <div class="field--item"> <div class="paragraph paragraph--type--language-links paragraph-id--123 paragraph--view-mode--default"> <div class="language-switcher-main"> <span class="label-text"> <div class="field field--name-field-label field--type-string field--label-hidden field--item">United Kingdom</div> </span><span class="link-text"> <div class="field field--name-field-link1 field--type-link field--label-hidden field--items"> <div class="field--item"><a href="/alnylam-uk">English</a></div> </div> </span> </div> </div> </div> <div class="field--item"> <div class="paragraph paragraph--type--language-links paragraph-id--122 paragraph--view-mode--default"> <div class="language-switcher-main"> <span class="label-text"> <div class="field field--name-field-label field--type-string field--label-hidden field--item">Italy</div> </span><span class="link-text"> <div class="field field--name-field-link1 field--type-link field--label-hidden field--items"> <div class="field--item"><a href="https://www.alnylam.it/">Italiano</a></div> </div> </span> </div> </div> </div> </div> </section> </div> </div> </div> </div> </header> <div id="maindiv" class="container-fluid"> <main id="midcontent-area" class="column main-content"> <div id="content"> <div class="region region-content"> <div data-drupal-messages-fallback class="hidden"></div> <article data-history-node-id="48" role="article" about="/our-science/the-science-of-rnai" typeof="schema:WebPage" class="page full clearfix"> <span property="schema:name" content="OUR SCIENCE" class="hidden"></span> <div class="content"> <div class="field field--name-field-add-section field--type-entity-reference-revisions field--label-hidden field--items"> <div class="field--item"> <div class="paragraph paragraph--type--sim paragraph-id--249 paragraph--view-mode--default"> <div id="simple-banner-wrapper"> <div class="simple-banner" style=""> <div class="field field--name-field-upload-image field--type-image field--label-hidden field--item"> <img src="/sites/default/files/2022-09/d-hero-our-science%402x.jpg" width="2560" height="768" alt="OUR SCIENCE" loading="lazy" typeof="foaf:Image" class="img-responsive" /> </div> </div> </div> </div> </div> <div class="field--item"> <div class="paragraph paragraph--type--banner-overlay-html-content paragraph-id--250 paragraph--view-mode--default"> <div class="banner-overlay-html-content-description--component " style="width:1130px; margin:auto;"> <div class="field field--name-field-body field--type-text-with-summary field--label-hidden field--item"><p class="mobile-eyebrow"><span class="our-science">Our Science</span></p> <h1 class="our-science text-align-center"><strong>OUR SCIENCE</strong></h1> <h2 class="text-align-center">Pioneering RNAi Therapeutics</h2> <p class="font-20 text-align-center margin-bottom-24px">RNAi therapeutics is an innovative new class of medicines based on RNA interference (RNAi)—a breakthrough discovery in understanding how genes are regulated naturally within cells. The significance of the discovery of RNAi was recognized with the 2006 Nobel Prize in Medicine or Physiology.</p> <p class="margin-bottom-24px">Since our founding in 2002, Alnylam has pioneered RNAi-based medicines through sustained research and development (R&D) efforts that have yielded the critical breakthroughs and innovations that make RNAi therapeutics possible. Nearly 15 years of R&D work delivered the world’s first approved RNAi therapeutic—ONPATTRO® (patisiran)—in 2018 and, subsequently, GIVLAARI® (givosiran), OXLUMO® (lumasiran), Leqvio® (inclisiran)*, and AMVUTTRA® (vutrisiran).</p> <p>Our <a href="/alnylam-rnai-pipeline/">robust pipeline</a> of investigational RNAi therapeutics is currently focused on several disease areas including transthyretin amyloidosis, rare diseases, cardiovascular diseases, metabolic diseases, and neurological diseases—and we are actively exploring other disease areas.</p> </div> </div> </div> </div> <div class="field--item"> <div class="paragraph paragraph--type--full-html-content-with-backgroun paragraph-id--254 paragraph--view-mode--default"> <div id="full-html-content-background" class="" style="background-color: #f4f9fc ;"> <div class="row inner-block" style="width:px; margin:auto;"> <div class="field field--name-field-html-content-bg field--type-entity-reference-revisions field--label-hidden field--items"> <div class="field--item"> <div class="paragraph paragraph--type--body paragraph-id--253 paragraph--view-mode--default"> <div class="description--component" style="width:975px; margin:auto; "> <div class="field field--name-field-body field--type-text-with-summary field--label-hidden field--item"><h2 class="text-align-center margin-bottom-24px">How RNAi Therapeutics Work</h2> <p class="margin-bottom-24px">Our medicines use RNA interference (RNAi) to “silence” or turn off the production of specific genes that cause disease or that contribute to disease.</p> <p class="margin-bottom-24px">RNAi is a natural biological process that regulates gene expression by “interfering” with messenger RNA (mRNA), which carries DNA’s instructions for making new proteins. Our RNAi therapeutics mimic this process by delivering specially designed small interfering RNAs (siRNAs) that, as part of RISC (RNA-induced silencing complex), bind to target disease-causing mRNA and guide their destruction like a pair of molecular scissors.</p> <p>By addressing genetically validated targets, our RNAi therapeutics work “upstream” of most other classes of medicines, such as small molecules and monoclonal antibodies.</p> <img alt="RNA interference (RNAi) pathway diagram – how RNAi therapeutics use siRNAs to target and degrade mRNA" class="desktop-view-img align-center" data-entity-type="file" data-entity-uuid="a81fef70-87cf-4f94-a3f6-c4a5787eebaa" src="/sites/default/files/inline-images/desktop.png" width="971" height="440" loading="lazy" /><p><img alt="rnai-img-tablet" class="mobile-view-img" data-entity-type="file" data-entity-uuid="22f0976a-1abd-4f2e-962e-65a6669a3b11" src="/sites/default/files/inline-images/the_rani_process.png" width="1125" height="2232" loading="lazy" /></p> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="field--item"> <div class="paragraph paragraph--type--full-html-light-banner-dark-bann paragraph-id--260 paragraph--view-mode--default"> <div id="full-html-light-dark" style="background: ;"> <div style="width: px; margin:auto;"> <div></div> <div class="field_fullhtml_light_dark_field"> <div class="field field--name-field-fullhtml-light-dark-field field--type-entity-reference-revisions field--label-hidden field--item"> <div class="paragraph paragraph--type--fullhtml-light-dark-banner-fiel paragraph--view-mode--default"> <div class="field field--name-field-full-html field--type-entity-reference-revisions field--label-hidden field--item"> <div class="paragraph paragraph--type--body paragraph-id--256 paragraph--view-mode--default"> <div class="description--component" style="width:975px; margin:auto; "> <div class="field field--name-field-body field--type-text-with-summary field--label-hidden field--item"><h2 class="text-align-center margin-bottom-24px">The Role of mRNA and siRNA</h2> <p class="margin-bottom-24px">Gene expression is the process by which a set of instructions in DNA are converted into proteins. Proteins are the “workers” in the biochemistry of life and are responsible for almost all body functions. They build and repair tissues; are critical to the development of the brain, heart, lung, liver, bones, muscles, cartilage, blood, and skin; and make up many body chemicals including enzymes and hormones. The genetic code for making proteins contained in the DNA directs the synthesis of a version of RNA called messenger RNA, or mRNA, which transports these instructions out of the nucleus of the cell (where DNA resides) into the cytoplasm of the cell where it is used by ribosomes to make new proteins.</p> <p>Sometimes, errors in the DNA, known as “mutations,” result in faulty mRNA that produce proteins that cause diseases. In these instances, our RNAi therapeutic approach leverages <a href="#how-siRNA-work">small interfering RNAs (siRNAs)</a> to target and degrade these specific mRNA. In other instances, our approach delivers therapeutic benefit by using siRNA to target and improve the levels of other, non–disease-causing proteins that are implicated in the disease pathway (ie, those that are not caused by a single genetic mutation). This second approach allows for the RNAi therapeutics to be used in a broader base of human diseases, such as hypercholesterolemia and hypertension.</p> </div> </div> </div> </div> <div class="field field--name-field-light-banner field--type-entity-reference-revisions field--label-hidden field--item"> <div class="paragraph paragraph--type--light-bg-banner paragraph-id--257 paragraph--view-mode--default"> </div> </div> <div class="field field--name-field-dark-banner field--type-entity-reference-revisions field--label-hidden field--item"> <div class="paragraph paragraph--type--dark-bg-banner paragraph-id--255 paragraph--view-mode--default" style="background-color:#00254B;" > <div id="dark-bg-banner" style="width:770px; margin:auto;"> <div class="row"> <div class="field field--name-field-description-text-area field--type-text-long field--label-hidden field--item"><div class="row our-science-irna-dark-bg"> <div class="col-sm-4"><img alt="sirna-molecule" data-entity-type="file" data-entity-uuid="2c1c86b2-8e1c-477e-97b3-a0c0d2c4892f" src="/sites/default/files/inline-images/sirna-molecule.png" width="245" height="176" loading="lazy" /></div> <div class="col-sm-8"> <p>siRNAs are double-stranded duplexes in which one strand is complementary to a given mRNA that encodes for a specific protein. Alnylam designs and “synthesizes” specific siRNAs that correspond to the target mRNA of the disease we want to treat.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="field_full_html_paragraph"> <div class="field field--name-field-full-html-para field--type-entity-reference-revisions field--label-hidden field--items"> <div class="field--item"> <div class="paragraph paragraph--type--body paragraph-id--259 paragraph--view-mode--default"> <div class="description--component" style="width:1025px; margin:auto; "> <div class="field field--name-field-body field--type-text-with-summary field--label-hidden field--item"><h5>We believe that siRNAs can be designed to target essentially any gene in the genome</h5> <p>Our ability to synthesize siRNAs, combined with our R&D product engine that features technology that makes our RNAi therapeutics highly reproducible and modular, opens up possibilities to address a wide variety of diseases, both rare and more common.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="field--item"> <div class="paragraph paragraph--type--video-popup paragraph-id--261 paragraph--view-mode--default"> <div class="video-popup-content" style="width:850px; margin:auto;"> <a data-colorbox-inline=".video-box-261" style="width: 571px; height:326px;"> <div class="three-column-image-box"> <div class="field field--name-field-upload-image field--type-image field--label-hidden field--item"> <img src="/sites/default/files/2022-09/video-large-w-descriptor-our-science_0.jpg" width="850" height="480" alt="How RNA Interference (RNAi) Works – Video" loading="lazy" typeof="foaf:Image" class="img-responsive" /> </div> <div class="three-column-video-play-button"></div> </div> <div class="video-box-261" style="display: none;"> <div class="field field--name-field-embed-video field--type-video-embed-field field--label-hidden field--item"><div class="video-embed-field-provider-youtube video-embed-field-responsive-video form-group"><iframe width="854" height="480" frameborder="0" allowfullscreen="allowfullscreen" src="https://www.youtube.com/embed/ggVVhj88KQI?autoplay=0&start=0&rel=0"></iframe> </div> </div> </div> </a> <div class="video-popup-desc"> <div class="field field--name-field-video-desc field--type-text-long field--label-hidden field--item"><p class="text-align-center"><strong>Take a Deeper Look: The RNAi Therapeutic Mechanism of Action</strong></p> </div> </div> </div> </div> </div> <div class="field--item"> <div class="paragraph paragraph--type--full-html-content-with-backgroun paragraph-id--263 paragraph--view-mode--default"> <div id="full-html-content-background" class="" style="background-color: #f4f9fc ;"> <div class="row inner-block" style="width:px; margin:auto;"> <div class="field field--name-field-html-content-bg field--type-entity-reference-revisions field--label-hidden field--items"> <div class="field--item"> <div class="paragraph paragraph--type--body paragraph-id--262 paragraph--view-mode--default"> <div class="description--component" style="width:975px; margin:auto; "> <div class="field field--name-field-body field--type-text-with-summary field--label-hidden field--item"><div id="how-siRNA-work"> <h2 class="text-align-center">How siRNAs Work</h2> <p class="margin-bottom-24px">When the siRNA duplex is <a href="/our-science/sirna-delivery-platforms/">delivered</a> into the cell, it is recognized by a protein complex known as the RNA-induced silencing complex (RISC), which already resides in the cell as a primary component of the natural RNAi pathway. Our siRNA duplex is recognized by and loaded into RISC, which removes one of the two strands (the “passenger” strand). This functional RISC now has only the complementary (or “guide”) strand that stays bound to the RISC, helping it find and pair with its matching (or “complementary”) mRNA before it is converted into a protein by a ribosome. Once the match is found, like a pair of molecular scissors, the siRNA together with RISC cleaves the “unwanted” target mRNA, causing it to be degraded. This process is catalytic, meaning that a single siRNA-loaded RISC can degrade many copies of the target mRNA. As a result, the production of the specific “unwanted” protein that corresponds to that mRNA is reduced or “silenced.”</p> <p class="margin-bottom-24px">Additionally, we believe that siRNAs can be developed to address infectious diseases by directly targeting viral RNA or their host factors for destruction such that the virus is unable make copies of itself or to get inside cells in the first place.</p> <h3>Key features of our RNAi therapeutics:</h3> <ul><li>Ability to target potentially any gene in the genome, including targets that are “undruggable” by small molecules and antibodies</li> <li>Highly potent and durable effect (dosing as infrequently as biannual or annual)</li> <li>Administration through multiple routes—intravenous (IV), subcutaneous, and inhalation delivery</li> <li>Demonstrated clinical benefit with a lower dose and dose frequency, and an encouraging overall safety profile compared to other approaches to gene silencing</li> <li>Modular, reproducible, and consistent performance across organs and diseases</li> </ul></div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="field--item"> <div class="paragraph paragraph--type--icon-copy-link-list paragraph-id--318 paragraph--view-mode--default"> <div class="icon-copy-link-list" style="background:; margin:auto;"> <div style="width:975px; margin:auto;"> <div class="field field--name-field-icon-copy-link-list-feilds field--type-entity-reference-revisions field--label-hidden field--items"> <div class="field--item"> <div class="paragraph paragraph--type--icon-copy-link-list-feilds paragraph-id--316 paragraph--view-mode--default"> <div class="icon-copy-link-list-feilds"> <div class="row"> <div class="col-sm-3"> <div class="icon"> <div class="field field--name-field-default-icon field--type-image field--label-hidden field--item"> <img src="/sites/default/files/2022-03/icons-molecule-144-x-144.svg" alt="" loading="lazy" typeof="foaf:Image" class="img-responsive" /> </div> </div> </div> <div class="col-sm-9"> <h3> <div class="field field--name-field-heading-1 field--type-string field--label-hidden field--item">OUR siRNA DELIVERY PLATFORMS</div> </h3> <div class="desc"> <div class="field field--name-field-description-text-area field--type-text-long field--label-hidden field--item"><p class="widget"><span class="widget-line-our-science"> </span></p> <p>In order for siRNAs to target and disable mRNA involved in the cause or “pathway” of disease, they must be specifically and efficiently delivered to the tissue where the production of proteins encoded by a specific gene takes place. Solving for delivery was one of the primary obstacles that Alnylam scientists had to overcome in pioneering this new class of medicines.</p> <p><a href="/our-science/sirna-delivery-platforms/">Learn More ›</a></p> </div> </div> </div> </div> </div> </div> </div> <div class="field--item"> <div class="paragraph paragraph--type--icon-copy-link-list-feilds paragraph-id--317 paragraph--view-mode--default"> <div class="icon-copy-link-list-feilds"> <div class="row"> <div class="col-sm-3"> <div class="icon"> <div class="field field--name-field-default-icon field--type-image field--label-hidden field--item"> <img src="/sites/default/files/2021-11/Human_Genetics_Logo.png" width="244" height="54" alt="" loading="lazy" typeof="foaf:Image" class="img-responsive" /> </div> </div> </div> <div class="col-sm-9"> <h3> <div class="field field--name-field-heading-1 field--type-string field--label-hidden field--item">LEVERAGING GENETICS TO ACCELERATE DRUG DEVELOPMENT</div> </h3> <div class="desc"> <div class="field field--name-field-description-text-area field--type-text-long field--label-hidden field--item"><p class="widget"><span class="widget-line-our-science"> </span></p> <p class="margin-bottom-32px">The Alnylam Human Genetics group is leveraging large sets of genetic data, the latest analytical and computational technologies, the expertise of a multi-disciplinary team and strategic partnerships, to disrupt the traditional drug discovery and development process. 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