CINXE.COM

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id="mobile-main-menu-menu-link-content369c2613-4f95-495f-b97d-7fe7704c1281" class="sf-depth-2 sf-no-children"><a href="https://investors.alnylam.com/press-releases" class="sf-depth-2 sf-external">Press Releases</a></li><li id="mobile-main-menu-menu-link-content9624843b-3ef8-4260-97fc-4719352453f5" class="sf-depth-2 sf-no-children"><a href="https://capella.alnylam.com/our-science/capella-rnai-innovation/" class="sf-depth-2 sf-external">Capella (Scientific Presentations)</a></li><li id="mobile-main-menu-menu-link-content8852cdce-87dc-4c88-be02-219bdc7a435f" class="sf-depth-2 sf-no-children"><a href="https://www.rnaiscience.com/" class="sf-depth-2 sf-external" target="_blank">Medical Resources (RNAi Science)</a></li><li id="mobile-main-menu-menu-link-content54fe53ea-8cc4-4734-9e8b-b9e23b3774a0" class="sf-depth-2 sf-no-children"><a href="/contact-us" class="sf-depth-2">Contact Us</a></li></ul></li> </ul> </section> </div> </div> <div class="mobile-header-logo"> <div class="region 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class="field--item"><a href="/">English</a></div> </div> </span> </div> </div> </div> <div class="field--item"> <div class="paragraph paragraph--type--language-links paragraph-id--108 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">Austria</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-austria">Deutsch</a></div> </div> </span> </div> </div> </div> <div class="field--item"> <div class="paragraph paragraph--type--language-links paragraph-id--124 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">Japan</div> </span><span class="link-text"> <div class="field field--name-field-link1 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Republic</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-czech-republic">Čeština</a></div> </div> </span> </div> </div> </div> <div class="field--item"> <div class="paragraph paragraph--type--language-links paragraph-id--115 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">Spain </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-espana">Español</a></div> </div> </span> </div> </div> </div> <div class="field--item"> <div class="paragraph paragraph--type--language-links paragraph-id--116 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">Denmark </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-denmark">Dansk</a></div> </div> </span> </div> </div> </div> <div class="field--item"> <div class="paragraph paragraph--type--language-links paragraph-id--117 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">Sweden</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-sverige">Svenska</a></div> </div> </span> </div> </div> </div> <div class="field--item"> <div class="paragraph paragraph--type--language-links paragraph-id--118 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">France</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.fr/">Français</a></div> </div> </span> </div> </div> </div> <div class="field--item"> <div class="paragraph paragraph--type--language-links paragraph-id--119 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">Switzerland</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-switzerland-french">Français</a></div> <div class="field--item"><a href="/alnylam-switzerland-german">Deutsch</a></div> 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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> <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" class="sf-depth-2 sf-no-children"><a href="https://investors.alnylam.com/" class="sf-depth-2 sf-external">For Investors</a></li><li id="top-navigation-menu-link-contente1e1fcab-d6cb-4681-aec8-647dac1fe8f2" class="sf-depth-2 sf-no-children"><a href="https://investors.alnylam.com/alny-stock-information" class="sf-depth-2 sf-external">Stock Information</a></li><li id="top-navigation-menu-link-content37980c4c-fa7d-430a-9bb6-13addbb93796" class="sf-depth-2 sf-no-children"><a href="https://investors.alnylam.com/investor-toolkit" class="sf-depth-2 sf-external">Investors Toolkit</a></li><li id="top-navigation-menu-link-content8f5bcff2-d5da-45e2-b6df-8bb846a4edc4" class="sf-depth-2 sf-no-children"><a href="https://investors.alnylam.com/events" class="sf-depth-2 sf-external">Events & Presentations</a></li><li id="top-navigation-menu-link-content1cbbc9bd-ff86-41f1-b059-9004baaceb84" class="sf-depth-2 sf-no-children"><a href="https://investors.alnylam.com/financial-information" class="sf-depth-2 sf-external">Financial Information</a></li><li id="top-navigation-menu-link-content7a928654-3535-49aa-a4db-ba6e25e4c2a4" class="sf-depth-2 sf-no-children"><a href="https://investors.alnylam.com/financial-information?sec=#sec_filings" class="sf-depth-2 sf-external">SEC Filings</a></li><li 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<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="51" role="article" about="/our-science/sirna-delivery-platforms" typeof="schema:WebPage" class="page full clearfix"> <span property="schema:name" content="DELIVERY PLATFORMS" 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--275 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/2021-11/our-science-delivery-platforms-hero_2560x768.jpg" width="2560" height="768" alt="DELIVERY PLATFORMS" 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--276 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 margin-bottom-24px"><strong>DELIVERY PLATFORMS</strong></h1> <p class="font-20 text-align-center margin-bottom-24px">Our RNA interference (RNAi) therapeutics utilize two distinct approaches to enable delivery of small interfering RNA (siRNA) to target tissues—<a href="#lnps">lipid nanoparticles (LNPs)</a> and <a href="#conjugates" id="conjugates-link">conjugates</a>. We are continually improving and expanding our novel delivery systems and applying them to new organs and diseases.</p> <p class="margin-bottom-24px">Our RNAi therapeutics utilize specially designed <a href="/our-science/the-science-of-rnai/#how-siRNA-works">siRNA </a>to seek out and disable messenger RNA (mRNA) involved in the cause or “pathway” of diseases, therefore “interfering” with gene transcription. But for these siRNA to reach the target mRNA, they must be precisely and efficiently delivered to the tissue where the mRNA are converted to proteins. Alnylam scientists have pioneered the use of LNPs and conjugates for drug delivery.<a id="lnps" name="lnps"></a></p> <p>Learn more about <a href="/our-science/the-science-of-rnai/">the science of RNAi therapeutics</a>.<a id="lnps" name="lnps"></a></p> </div> </div> </div> </div> <div class="field--item"> <div class="paragraph paragraph--type--full-html-content-with-backgroun paragraph-id--278 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--277 paragraph--view-mode--default"> <div class="description--component" style="width:1132px; 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">Lipid Nanoparticles (LNPs)</h2> <p class="margin-bottom-24px">Lipid nanoparticles (LNPs) are chemically synthesized multicomponent lipid formulations (~100 nm in size) encapsulating siRNAs for delivery to the target tissue. En route to their destination, the siRNAs encapsulated in LNPs are protected against degradation by ubiquitous nucleases. The LNPs used by Alnylam preferentially distribute to the liver because of their affinity for apolipoprotein E (apoE), an endogenous ligand for the low-density lipoprotein receptor (LDLR) expressed on the surface of liver cells (hepatocytes).</p> <p class="margin-bottom-24px">RNAi therapeutics utilizing LNP technology are administered intravenously (IV). Our first approved RNAi therapeutic, ONPATTRO® (patisiran), utilizes LNP-based delivery.</p> <p class="margin-bottom-32px">We are proud to see that our pioneering work in the use of LNPs for drug delivery has been utilized by several of our biopharmaceutical peers for the development of vaccines for COVID-19, the disease caused by SARS-CoV-2.</p> <img alt="LNPS" class="desktop-view-img align-center" data-entity-type="file" data-entity-uuid="2d2f8062-04c4-408c-8611-9a9f4a8b3e01" src="/sites/default/files/inline-images/d-lnp-graphic.png" /><img alt="LNPS" class="mobile-view-img align-center" data-entity-type="file" data-entity-uuid="818f713c-7d85-4bbe-8e81-e74fc05f1bae" src="/sites/default/files/inline-images/cellmembrane.png" /></div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="field--item"> <div class="paragraph paragraph--type--full-html-content-with-backgroun paragraph-id--281 paragraph--view-mode--default"> <div id="full-html-content-background" class="" style="background-color: ;"> <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--280 paragraph--view-mode--default"> <div class="description--component" style="width:1132px; margin:auto; "> <div class="field field--name-field-body field--type-text-with-summary field--label-hidden field--item"><p style="margin:0;"><a id="conjugates" name="conjugates"></a></p> <h2 class="text-align-center margin-bottom-24px">Conjugates</h2> <p class="margin-bottom-24px">Conjugates are defined single chemical entities with fully modified siRNA conjugated to targeting ligand to help them find their way to a specific cell or tissue within the body. Conjugates are a “lock and key” system, where the lock is the receptor found on the target cell and the key is the ligand attached to the siRNA.</p> <p class="margin-bottom-24px">We leverage two conjugate approaches to enable targeted delivery to the liver and the central nervous system (CNS)—GalNAc conjugates and CNS-targeted siRNA conjugates.</p> <p class="margin-bottom-24px"><strong>GalNAc conjugates</strong> – GalNAc, or N-acetylgalactosamine, is a sugar molecule that can recognize and bind to a cell surface protein, the asialoglycoprotein receptor (ASGPR), which is abundantly expressed on liver cells (hepatocytes). The binding affinity to the receptor increases exponentially if several GalNAc units are combined into a multivalent ligand. Our GalNAc-conjugated siRNAs are trivalent, meaning that three GalNAc molecules are clustered and conjugated to one siRNA molecule. This setup guarantees high affinity (strength) of the interaction between ASGPR and the GalNAc ligand, thus promoting optimal efficiency of siRNA delivery to the liver.</p> <p class="margin-bottom-24px">RNAi therapeutics utilizing GalNAc conjugate technology are administered subcutaneously. Our medicines GIVLAARI® (givosiran), OXLUMO® (lumasiran), <span class="white-space">AMVUTTRA® (vutrisiran)</span>, and Leqvio® (inclisiran)* utilize GalNAc conjugate delivery.</p> <img alt="lipid-graphics" class="desktop-view-img align-center" data-entity-type="file" data-entity-uuid="97f6cd91-ad89-486b-89f0-28128417d0e4" src="/sites/default/files/inline-images/lipid-nanoparticles-graphic-1.png" width="1000" height="612" loading="lazy" /><p> </p> <img alt="lipid-graphics" class="mobile-view-img align-center" data-entity-type="file" data-entity-uuid="d1c4729b-3fb8-47bb-b710-0a04f44e940b" src="/sites/default/files/inline-images/conjugates.png" /><p> </p> <p class="margin-bottom-24px"><strong>C16 conjugates</strong> – The 2’-O-hexadecyl (C16) is a short lipid chain attached to siRNA that provides lipophilicity to interact with cell membrane or membrane proteins for uptake in multiple cell types, including the cells of the central nervous system (CNS), the lung and eye.</p> <p class="margin-bottom-24px">ALN-APP, our investigational RNAi therapeutic targeting amyloid precursor protein in Phase 1 development (in collaboration with Regeneron Pharmaceuticals) for the treatment of Alzheimer’s disease and cerebral amyloid angiopathy, utilizes C16 conjugate technology. ALN-APP is administered intrathecally (via an injection into the spinal cord).</p> <img alt="lipid-graphics" class="desktop-view-img align-center" data-entity-type="file" data-entity-uuid="8b59d401-ccc1-4057-ad88-76ec53e424ef" src="/sites/default/files/inline-images/C16_Conjugate.png" /><p> </p> <img alt="lipid-graphics" class="mobile-view-img align-center" data-entity-type="file" data-entity-uuid="340333a4-449a-4000-af12-755f8c3c8b30" src="/sites/default/files/inline-images/c-16-diagram-for-mobile.png" /><p>*Licensed to Novartis</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="field--item"> <div class="paragraph paragraph--type--_-column-card paragraph-id--284 paragraph--view-mode--default"> <div id="two-column-card" style="background: rgba(185, 217, 235, 0.16);"> <div style="width: 1170px; margin:auto;"> <div class="field field--name-field-heading-image-description field--type-entity-reference-revisions field--label-hidden field--items"> <div 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