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2021 | TRON Translational Oncology Mainz | Connecting Competence

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(2021) A noninflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis.聽 Science. 371(6525):145-153. DOI, PMID [su_spoiler title=Show abstract]The ability to control autoreactive T cells without inducing systemic immune suppression is the major goal for treatment of autoimmune diseases. The key challenge is the safe and efficient delivery of pharmaceutically well-defined antigens in a noninflammatory context. Here, we show that systemic delivery of nanoparticle-formulated 1 methylpseudouridine-modified messenger RNA (m1唯 mRNA) coding for disease-related autoantigens results in antigen presentation on splenic CD11c+聽antigen-presenting cells in the absence of costimulatory signals. In several mouse models of multiple sclerosis, the disease is suppressed by treatment with such m1唯 mRNA. The treatment effect is associated with a reduction of effector T cells and the development of regulatory T cell (Treg聽cell) populations. Notably, these Treg聽cells execute strong bystander immunosuppression and thus improve disease induced by cognate and noncognate autoantigens. 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class="side-nav"> <ul class="nav-search"> <li> <a class="search-contents" href="#"></a> <ul> <li> <div class="widget widget_search"><div class="search_main"> <form method="get" class="searchform" action="https://web.archive.org/web/20210320060833/https://tron-mainz.de/de/"> <input type="text" class="field s" name="s" value="Search..." onfocus="if (this.value == 'Search...') {this.value = '';}" onblur="if (this.value == '') {this.value = 'Search...';}"/> <button type="submit" class="fa fa-search submit" name="submit" value="Search"></button> </form> <div class="fix"></div> </div></div> </li> </ul> </li> </ul> </div><!-- /#side-nav --> </section><!-- /.menus --> <a href="#top" class="nav-close"> <i class="fa fa-times"></i> <span>Return to Content</span> </a> </nav> </div><!--/#nav-container--> </header> </div><!--/#header-container--> <!-- #content Starts --> <div id="content" class="col-full"> <div id="main-sidebar-container"> <!-- #main Starts --> <section id="main"> <article class="post-9286 page type-page status-publish has-post-thumbnail hentry category-home-grid category-publications"> <header> <h1 class="title entry-title">2021</h1> </header> <section class="entry"> <div class="vc_row wpb_row vc_row-fluid vc_column-gap-15 mpc-row"> <!-- /wp:shortcode --> <mpc__ wp_paragraph--> <div class="wpb_column vc_column_container vc_col-sm-9 mpc-column" data-column-id="mpc_column-56055916201a70"><div class="vc_column-inner"><div class="wpb_wrapper"> <div class="wpb_text_column wpb_content_element "> <div class="wpb_wrapper"> <p><!-- /wp:paragraph --></p> <p><mpc__ wp_paragraph--></mpc__></p> <p>&nbsp; Krienke C, Kolb L, Diken E, Streuber M, Kirchhoff S, Bukur T, Akilli-&Ouml;zt&uuml;rk &Ouml;, Kranz LM, Berger H, Petschenka J, Diken M, Kreiter S, Yogev N, Waisman A, Karik&oacute; K, T&uuml;reci &Ouml;, Sahin U. (2021) <strong>A noninflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis</strong>.&nbsp; <em>Science</em>. 371(6525):145-153. <a href="https://web.archive.org/web/20210320060833/https://science.sciencemag.org/content/371/6525/145">DOI</a>, <a href="https://web.archive.org/web/20210320060833/https://pubmed.ncbi.nlm.nih.gov/33414215/">PMID</a> </p><div class="su-spoiler su-spoiler-style-default su-spoiler-icon-plus su-spoiler-closed" data-scroll-offset="0" data-anchor-in-url="no"><div class="su-spoiler-title" tabindex="0" role="button"><span class="su-spoiler-icon"></span>Show abstract</div><div class="su-spoiler-content su-u-clearfix su-u-trim">The ability to control autoreactive T cells without inducing systemic immune suppression is the major goal for treatment of autoimmune diseases. The key challenge is the safe and efficient delivery of pharmaceutically well-defined antigens in a noninflammatory context. Here, we show that systemic delivery of nanoparticle-formulated 1 methylpseudouridine-modified messenger RNA (m1&Psi; mRNA) coding for disease-related autoantigens results in antigen presentation on splenic CD11c<sup>+</sup>&nbsp;antigen-presenting cells in the absence of costimulatory signals. In several mouse models of multiple sclerosis, the disease is suppressed by treatment with such m1&Psi; mRNA. The treatment effect is associated with a reduction of effector T cells and the development of regulatory T cell (T<sub>reg</sub>&nbsp;cell) populations. Notably, these T<sub>reg</sub>&nbsp;cells execute strong bystander immunosuppression and thus improve disease induced by cognate and noncognate autoantigens. </div></div> &nbsp; <p><!-- /wp:paragraph --></p> <p><mpc__ wp_paragraph--></mpc__></p> </div> </div> </div></div></div><div class="wpb_column vc_column_container vc_col-sm-3 mpc-column"><div class="vc_column-inner"><div class="wpb_wrapper"> <div class="vc_grid-container-wrapper vc_clearfix"> <div class="vc_grid-container vc_clearfix wpb_content_element vc_basic_grid" data-initial-loading-animation="fadeIn" data-vc-grid-settings="{&quot;page_id&quot;:9286,&quot;style&quot;:&quot;all&quot;,&quot;action&quot;:&quot;vc_get_vc_grid_data&quot;,&quot;shortcode_id&quot;:&quot;1516780861471-483aff06-d626-10&quot;,&quot;tag&quot;:&quot;vc_basic_grid&quot;}" data-vc-request="https://tron-mainz.de/de/wp-admin/admin-ajax.php" data-vc-post-id="9286" data-vc-public-nonce="660a59436e"> <style 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#ffffff;text-align: center;font-family:Lato;font-weight:700;font-style:normal"><a href="https://web.archive.org/web/20210320060833/https://tron-mainz.de/de/2016-2/" class="vc_gitem-link" title="2016">2016</a></h3></div></div></div></div></div><div class="vc_gitem-zone vc_gitem-zone-b vc_custom_1484317192348 vc-gitem-zone-height-mode-auto vc_gitem-is-link"><a href="https://web.archive.org/web/20210320060833/https://tron-mainz.de/de/2016-2/" title="2016" class="vc_gitem-link vc-zone-link"></a><div class="vc_gitem-zone-mini"><div class="vc_gitem_row vc_row vc_gitem-row-position-middle"><div class="vc_col-sm-12 vc_gitem-col vc_gitem-col-align-"><div class="vc_custom_heading sidegrid vc_custom_1486920211292 vc_gitem-post-data vc_gitem-post-data-source-post_title"><h3 style="color: #ffffff;text-align: center;font-family:Lato;font-weight:700;font-style:normal"><a href="https://web.archive.org/web/20210320060833/https://tron-mainz.de/de/2016-2/" class="vc_gitem-link" title="2016">2016</a></h3></div></div></div></div></div></div></div><div class="vc_clearfix"></div></div><div class="vc_grid-item vc_clearfix vc_col-sm-12"><div class="vc_grid-item-mini vc_clearfix "><div class="vc_gitem-animated-block vc_gitem-animate vc_gitem-animate-none" data-vc-animation="none"><div class="vc_gitem-zone vc_gitem-zone-a vc_custom_1484316837418 vc-gitem-zone-height-mode-auto vc-gitem-zone-height-mode-auto-16-9 vc_gitem-is-link"><a href="https://web.archive.org/web/20210320060833/https://tron-mainz.de/de/2015-2/" title="2015" class="vc_gitem-link vc-zone-link"></a><div class="vc_gitem-zone-mini"><div class="vc_gitem_row vc_row vc_gitem-row-position-middle"><div class="vc_col-sm-12 vc_gitem-col vc_gitem-col-align-"><div class="vc_custom_heading sidegrid vc_custom_1486920202167 vc_gitem-post-data vc_gitem-post-data-source-post_title"><h3 style="color: #ffffff;text-align: center;font-family:Lato;font-weight:700;font-style:normal"><a 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class="vc_clearfix"></div></div><div class="vc_grid-item vc_clearfix vc_col-sm-12"><div class="vc_grid-item-mini vc_clearfix "><div class="vc_gitem-animated-block vc_gitem-animate vc_gitem-animate-none" data-vc-animation="none"><div class="vc_gitem-zone vc_gitem-zone-a vc_custom_1484316837418 vc-gitem-zone-height-mode-auto vc-gitem-zone-height-mode-auto-16-9 vc_gitem-is-link"><a href="https://web.archive.org/web/20210320060833/https://tron-mainz.de/de/2014-2/" title="2014" class="vc_gitem-link vc-zone-link"></a><div class="vc_gitem-zone-mini"><div class="vc_gitem_row vc_row vc_gitem-row-position-middle"><div class="vc_col-sm-12 vc_gitem-col vc_gitem-col-align-"><div class="vc_custom_heading sidegrid vc_custom_1486920202167 vc_gitem-post-data vc_gitem-post-data-source-post_title"><h3 style="color: #ffffff;text-align: center;font-family:Lato;font-weight:700;font-style:normal"><a href="https://web.archive.org/web/20210320060833/https://tron-mainz.de/de/2014-2/" class="vc_gitem-link" 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class="vc_gitem-animated-block vc_gitem-animate vc_gitem-animate-none" data-vc-animation="none"><div class="vc_gitem-zone vc_gitem-zone-a vc_custom_1484316837418 vc-gitem-zone-height-mode-auto vc-gitem-zone-height-mode-auto-16-9 vc_gitem-is-link"><a href="https://web.archive.org/web/20210320060833/https://tron-mainz.de/de/publications/2013-2/" title="2013" class="vc_gitem-link vc-zone-link"></a><div class="vc_gitem-zone-mini"><div class="vc_gitem_row vc_row vc_gitem-row-position-middle"><div class="vc_col-sm-12 vc_gitem-col vc_gitem-col-align-"><div class="vc_custom_heading sidegrid vc_custom_1486920202167 vc_gitem-post-data vc_gitem-post-data-source-post_title"><h3 style="color: #ffffff;text-align: center;font-family:Lato;font-weight:700;font-style:normal"><a href="https://web.archive.org/web/20210320060833/https://tron-mainz.de/de/publications/2013-2/" class="vc_gitem-link" title="2013">2013</a></h3></div></div></div></div></div><div class="vc_gitem-zone vc_gitem-zone-b vc_custom_1484317192348 vc-gitem-zone-height-mode-auto vc_gitem-is-link"><a href="https://web.archive.org/web/20210320060833/https://tron-mainz.de/de/publications/2013-2/" title="2013" class="vc_gitem-link vc-zone-link"></a><div class="vc_gitem-zone-mini"><div class="vc_gitem_row vc_row vc_gitem-row-position-middle"><div class="vc_col-sm-12 vc_gitem-col vc_gitem-col-align-"><div class="vc_custom_heading sidegrid vc_custom_1486920211292 vc_gitem-post-data vc_gitem-post-data-source-post_title"><h3 style="color: #ffffff;text-align: center;font-family:Lato;font-weight:700;font-style:normal"><a href="https://web.archive.org/web/20210320060833/https://tron-mainz.de/de/publications/2013-2/" class="vc_gitem-link" title="2013">2013</a></h3></div></div></div></div></div></div></div><div class="vc_clearfix"></div></div><div class="vc_grid-item vc_clearfix vc_col-sm-12"><div class="vc_grid-item-mini vc_clearfix "><div class="vc_gitem-animated-block vc_gitem-animate vc_gitem-animate-none" data-vc-animation="none"><div class="vc_gitem-zone vc_gitem-zone-a vc_custom_1484316837418 vc-gitem-zone-height-mode-auto vc-gitem-zone-height-mode-auto-16-9 vc_gitem-is-link"><a href="https://web.archive.org/web/20210320060833/https://tron-mainz.de/de/publications/2012-2/" title="2012" class="vc_gitem-link vc-zone-link"></a><div class="vc_gitem-zone-mini"><div class="vc_gitem_row vc_row vc_gitem-row-position-middle"><div class="vc_col-sm-12 vc_gitem-col vc_gitem-col-align-"><div class="vc_custom_heading sidegrid vc_custom_1486920202167 vc_gitem-post-data vc_gitem-post-data-source-post_title"><h3 style="color: #ffffff;text-align: center;font-family:Lato;font-weight:700;font-style:normal"><a href="https://web.archive.org/web/20210320060833/https://tron-mainz.de/de/publications/2012-2/" class="vc_gitem-link" title="2012">2012</a></h3></div></div></div></div></div><div class="vc_gitem-zone vc_gitem-zone-b vc_custom_1484317192348 vc-gitem-zone-height-mode-auto vc_gitem-is-link"><a 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vc_custom_1484316837418 vc-gitem-zone-height-mode-auto vc-gitem-zone-height-mode-auto-16-9 vc_gitem-is-link"><a href="https://web.archive.org/web/20210320060833/https://tron-mainz.de/de/publications/2011-2/" title="2011" class="vc_gitem-link vc-zone-link"></a><div class="vc_gitem-zone-mini"><div class="vc_gitem_row vc_row vc_gitem-row-position-middle"><div class="vc_col-sm-12 vc_gitem-col vc_gitem-col-align-"><div class="vc_custom_heading sidegrid vc_custom_1486920202167 vc_gitem-post-data vc_gitem-post-data-source-post_title"><h3 style="color: #ffffff;text-align: center;font-family:Lato;font-weight:700;font-style:normal"><a href="https://web.archive.org/web/20210320060833/https://tron-mainz.de/de/publications/2011-2/" class="vc_gitem-link" title="2011">2011</a></h3></div></div></div></div></div><div class="vc_gitem-zone vc_gitem-zone-b vc_custom_1484317192348 vc-gitem-zone-height-mode-auto vc_gitem-is-link"><a 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