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Elovl1 inhibition reduced very long chain fatty acids in a mouse model of adrenoleukodystrophy | bioRxiv
<!DOCTYPE html> <html lang="en" dir="ltr" xmlns="http://www.w3.org/1999/xhtml" xmlns:mml="http://www.w3.org/1998/Math/MathML"> <head prefix="og: http://ogp.me/ns# article: http://ogp.me/ns/article# book: http://ogp.me/ns/book#" > <!--[if IE]><![endif]--> <link rel="dns-prefetch" href="//d33xdlntwy0kbs.cloudfront.net" /> <link rel="dns-prefetch" href="//www.google.com" /> <link rel="dns-prefetch" href="//scholar.google.com" /> <link rel="dns-prefetch" href="//www.googletagmanager.com" /> <meta http-equiv="Content-Type" content="text/html; charset=utf-8" /> <link rel="shortcut icon" href="https://www.biorxiv.org/sites/default/files/images/favicon.ico" type="image/vnd.microsoft.icon" /> <meta name="viewport" content="width=device-width, initial-scale=1" /> <link rel="alternate" type="application/pdf" title="Full Text (PDF)" href="/content/10.1101/2024.11.11.622837v1.full.pdf" /> <link rel="alternate" type="text/plain" title="Full Text (Plain)" href="/content/10.1101/2024.11.11.622837v1.full.txt" /> <meta name="type" content="article" /> <meta name="category" content="article" /> <meta name="HW.identifier" content="/biorxiv/early/2024/11/11/2024.11.11.622837.atom" /> <meta name="HW.pisa" content="biorxiv;2024.11.11.622837v1" /> <meta name="DC.Format" content="text/html" /> <meta name="DC.Language" content="en" /> <meta name="DC.Title" content="Elovl1 inhibition reduced very long chain fatty acids in a mouse model of adrenoleukodystrophy" /> <meta name="DC.Identifier" content="10.1101/2024.11.11.622837" /> <meta name="DC.Date" content="2024-11-11" /> <meta name="DC.Publisher" content="Cold Spring Harbor Laboratory" /> <meta name="DC.Rights" content="© 2024, Posted by Cold Spring Harbor Laboratory. This pre-print is available under a Creative Commons License (Attribution-NonCommercial-NoDerivs 4.0 International), CC BY-NC-ND 4.0, as described at http://creativecommons.org/licenses/by-nc-nd/4.0/" /> <meta name="DC.AccessRights" content="restricted" /> <meta name="DC.Description" content="Adrenoleukodystrophy (ALD) is a rare neurometabolic disease caused by mutations in the ABCD1 gene, which encodes for the peroxisomal very long chain fatty acid (VLCFAs) transporter. It is a debilitating disorder, which has a spectrum of clinical presentations. The most severe form is a rapidly progressing demyelinating disease called cerebral ALD or CALD. Patients with cALD have a life expectancy of 2-4 years after onset and symptoms often manifest in childhood. The other forms are adrenomyeloneuropathy or AMN, which is a slower progressing degeneration of the spinal cord, and adrenal insufficiency (Addison disease). Since the accumulation of VLCFAs are a common factor in all ALD pathologies, we identified therapeutic approach that could correct this metabolic defect. We developed a substrate reduction therapy (SRT) for ALD in the form of an inhibitor of the lipid elongase principally responsible for the generation of VLCFAs, Elovl1. This small molecule was able to successfully reduce the accumulation of VLCFA in the brain and spinal cord of ABCD1 −/y mice. We used single nuclei RNA seq to identify the pathways altered in the ABCD1 −/y mouse and corrected with Elovl1 inhibition. Though many lipid metabolism genes and pathways were indeed corrected, treatment with the Elovl1 inhibitor unexpectedly led to profound transcriptional changes beyond correction of pathways altered by loss of ABCD1 . These data suggest that Elovl1 inhibition may have broader consequences in ABCD1 −/y mice than correction of lipid homeostasis. ### Competing Interest Statement All authors are Sanofi employees or were Sanofi employees when they contributed to this project" /> <meta name="DC.Contributor" content="Jeremy Y. Huang" /> <meta name="DC.Contributor" content="Brian Freed" /> <meta name="DC.Contributor" content="Martin Hanus" /> <meta name="DC.Contributor" content="Kelly Keefe" /> <meta name="DC.Contributor" content="Ming Sum Ruby Chiang" /> <meta name="DC.Contributor" content="Alexander Brezzani" /> <meta name="DC.Contributor" content="Yongyi Luo" /> <meta name="DC.Contributor" content="Yihang Li" /> <meta name="DC.Contributor" content="Becky Lam" /> <meta name="DC.Contributor" content="Stephanie Holley" /> <meta name="DC.Contributor" content="Joseph Gans" /> <meta name="DC.Contributor" content="Zuzana Dostalova" /> <meta name="DC.Contributor" content="Buyun Tang" /> <meta name="DC.Contributor" content="Clifford Phaneuf" /> <meta name="DC.Contributor" content="Erin Teeple" /> <meta name="DC.Contributor" content="Laura Parisi" /> <meta name="DC.Contributor" content="Lilu Guo" /> <meta name="DC.Contributor" content="Zhonglin Zhao" /> <meta name="DC.Contributor" content="Sofia N. Kinton" /> <meta name="DC.Contributor" content="Jacquelyn Dwyer" /> <meta name="DC.Contributor" content="Sandrine Teixeira" /> <meta name="DC.Contributor" content="Hong Ma" /> <meta name="DC.Contributor" content="Gary Asmussen" /> <meta name="DC.Contributor" content="Rajashree McLaren" /> <meta name="DC.Contributor" content="Donghui Wang" /> <meta name="DC.Contributor" content="Ann Baker" /> <meta name="DC.Contributor" content="Craig S. Siegel" /> <meta name="DC.Contributor" content="David Fink" /> <meta name="DC.Contributor" content="Kristen Randall" /> <meta name="DC.Contributor" content="Alexei Belenky" /> <meta name="DC.Contributor" content="Suchitra Venugopal" /> <meta name="DC.Contributor" content="Giorgio Gaglia" /> <meta name="DC.Contributor" content="Jennifer Johnson" /> <meta name="DC.Contributor" content="Dinesh S. Bangari" /> <meta name="DC.Contributor" content="S. Pablo Sardi" /> <meta name="DC.Contributor" content="Bailin Zhang" /> <meta name="DC.Contributor" content="Alexander Michel" /> <meta name="DC.Contributor" content="Jonathan D. Proto" /> <meta name="DC.Contributor" content="Alla Kloss" /> <meta name="DC.Contributor" content="Tatiana Gladysheva" /> <meta name="DC.Contributor" content="Can Kayatekin" /> <meta name="article:published_time" content="2024-11-11" /> <meta name="article:section" content="New Results" /> <meta name="citation_title" content="Elovl1 inhibition reduced very long chain fatty acids in a mouse model of adrenoleukodystrophy" /> <meta name="citation_abstract" lang="en" content="<p>Adrenoleukodystrophy (ALD) is a rare neurometabolic disease caused by mutations in the ABCD1 gene, which encodes for the peroxisomal very long chain fatty acid (VLCFAs) transporter. It is a debilitating disorder, which has a spectrum of clinical presentations. The most severe form is a rapidly progressing demyelinating disease called cerebral ALD or CALD. Patients with cALD have a life expectancy of 2-4 years after onset and symptoms often manifest in childhood. The other forms are adrenomyeloneuropathy or AMN, which is a slower progressing degeneration of the spinal cord, and adrenal insufficiency (Addison disease). Since the accumulation of VLCFAs are a common factor in all ALD pathologies, we identified therapeutic approach that could correct this metabolic defect. We developed a substrate reduction therapy (SRT) for ALD in the form of an inhibitor of the lipid elongase principally responsible for the generation of VLCFAs, Elovl1. This small molecule was able to successfully reduce the accumulation of VLCFA in the brain and spinal cord of ABCD1-/y mice. We used single nuclei RNA seq to identify the pathways altered in the ABCD1-/y mouse and corrected with Elovl1 inhibition. Though many lipid metabolism genes and pathways were indeed corrected, treatment with the Elovl1 inhibitor unexpectedly led to profound transcriptional changes beyond correction of pathways altered by loss of ABCD1. These data suggest that Elovl1 inhibition may have broader consequences in ABCD1-/y mice than correction of lipid homeostasis.</p>" /> <meta name="citation_journal_title" content="bioRxiv" /> <meta name="citation_publisher" content="Cold Spring Harbor Laboratory" /> <meta name="citation_publication_date" content="2024/01/01" /> <meta name="citation_mjid" content="biorxiv;2024.11.11.622837v1" /> <meta name="citation_id" content="2024.11.11.622837v1" /> <meta name="citation_public_url" content="https://www.biorxiv.org/content/10.1101/2024.11.11.622837v1" /> <meta name="citation_abstract_html_url" content="https://www.biorxiv.org/content/10.1101/2024.11.11.622837v1.abstract" /> <meta name="citation_full_html_url" content="https://www.biorxiv.org/content/10.1101/2024.11.11.622837v1.full" /> <meta name="citation_pdf_url" content="https://www.biorxiv.org/content/biorxiv/early/2024/11/11/2024.11.11.622837.full.pdf" /> <meta name="citation_doi" content="10.1101/2024.11.11.622837" /> <meta name="citation_num_pages" content="35" /> <meta name="citation_article_type" content="Article" /> <meta name="citation_section" content="New Results" /> <meta name="citation_firstpage" content="2024.11.11.622837" /> <meta name="citation_author" content="Jeremy Y. 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Nature 599, 102–107. 10.1038/s41586-021-03960-y." /> <meta name="twitter:title" content="Elovl1 inhibition reduced very long chain fatty acids in a mouse model of adrenoleukodystrophy" /> <meta name="twitter:site" content="@biorxivpreprint" /> <meta name="twitter:card" content="summary" /> <meta name="twitter:image" content="https://www.biorxiv.org/sites/default/files/images/biorxiv_logo_homepage7-5-small.png" /> <meta name="twitter:description" content="Adrenoleukodystrophy (ALD) is a rare neurometabolic disease caused by mutations in the ABCD1 gene, which encodes for the peroxisomal very long chain fatty acid (VLCFAs) transporter. It is a debilitating disorder, which has a spectrum of clinical presentations. The most severe form is a rapidly progressing demyelinating disease called cerebral ALD or CALD. Patients with cALD have a life expectancy of 2-4 years after onset and symptoms often manifest in childhood. The other forms are adrenomyeloneuropathy or AMN, which is a slower progressing degeneration of the spinal cord, and adrenal insufficiency (Addison disease). Since the accumulation of VLCFAs are a common factor in all ALD pathologies, we identified therapeutic approach that could correct this metabolic defect. We developed a substrate reduction therapy (SRT) for ALD in the form of an inhibitor of the lipid elongase principally responsible for the generation of VLCFAs, Elovl1. This small molecule was able to successfully reduce the accumulation of VLCFA in the brain and spinal cord of ABCD1 −/y mice. We used single nuclei RNA seq to identify the pathways altered in the ABCD1 −/y mouse and corrected with Elovl1 inhibition. Though many lipid metabolism genes and pathways were indeed corrected, treatment with the Elovl1 inhibitor unexpectedly led to profound transcriptional changes beyond correction of pathways altered by loss of ABCD1 . These data suggest that Elovl1 inhibition may have broader consequences in ABCD1 −/y mice than correction of lipid homeostasis. ### Competing Interest Statement All authors are Sanofi employees or were Sanofi employees when they contributed to this project" /> <meta name="og-title" property="og:title" content="Elovl1 inhibition reduced very long chain fatty acids in a mouse model of adrenoleukodystrophy" /> <meta name="og-url" property="og:url" content="https://www.biorxiv.org/content/10.1101/2024.11.11.622837v1" /> <meta name="og-site-name" property="og:site_name" content="bioRxiv" /> <meta name="og-description" property="og:description" content="Adrenoleukodystrophy (ALD) is a rare neurometabolic disease caused by mutations in the ABCD1 gene, which encodes for the peroxisomal very long chain fatty acid (VLCFAs) transporter. It is a debilitating disorder, which has a spectrum of clinical presentations. The most severe form is a rapidly progressing demyelinating disease called cerebral ALD or CALD. Patients with cALD have a life expectancy of 2-4 years after onset and symptoms often manifest in childhood. The other forms are adrenomyeloneuropathy or AMN, which is a slower progressing degeneration of the spinal cord, and adrenal insufficiency (Addison disease). Since the accumulation of VLCFAs are a common factor in all ALD pathologies, we identified therapeutic approach that could correct this metabolic defect. We developed a substrate reduction therapy (SRT) for ALD in the form of an inhibitor of the lipid elongase principally responsible for the generation of VLCFAs, Elovl1. This small molecule was able to successfully reduce the accumulation of VLCFA in the brain and spinal cord of ABCD1 −/y mice. We used single nuclei RNA seq to identify the pathways altered in the ABCD1 −/y mouse and corrected with Elovl1 inhibition. Though many lipid metabolism genes and pathways were indeed corrected, treatment with the Elovl1 inhibitor unexpectedly led to profound transcriptional changes beyond correction of pathways altered by loss of ABCD1 . These data suggest that Elovl1 inhibition may have broader consequences in ABCD1 −/y mice than correction of lipid homeostasis. ### Competing Interest Statement All authors are Sanofi employees or were Sanofi employees when they contributed to this project" /> <meta name="og-type" property="og:type" content="article" /> <meta name="og-image" property="og:image" content="https://www.biorxiv.org/sites/default/files/images/biorxiv_logo_homepage7-5-small.png" /> <meta name="citation_date" content="2024-11-11" /> <link rel="alternate" type="application/vnd.ms-powerpoint" title="Powerpoint" href="/content/10.1101/2024.11.11.622837v1.ppt" /> <meta name="description" content="bioRxiv - the preprint server for biology, operated by Cold Spring Harbor Laboratory, a research and educational institution" /> <meta name="generator" content="Drupal 7 (http://drupal.org)" /> <link rel="canonical" href="https://www.biorxiv.org/content/10.1101/2024.11.11.622837v1" /> <link rel="shortlink" 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id="zone-content" class="zone zone-content clearfix container-30"> <div class="grid-28 suffix-1 prefix-1 region region-content" id="region-content"> <div class="region-inner region-content-inner"> <a id="main-content"></a> <div class="block block-system block-main block-system-main odd block-without-title" id="block-system-main"> <div class="block-inner clearfix"> <div class="content clearfix"> <div class="panel-display panels-960-layout jcore-2col-layout" > <div class="panel-row-wrapper clearfix"> <div class="main-content-wrapper grid-17 suffix-1 alpha"> <div class="panel-panel panel-region-content"> <div class="inside"><div class="panel-pane pane-highwire-article-citation" > <div class="pane-content"> <div class="highwire-article-citation highwire-citation-type-highwire-article node4214327" data-node-nid="4214327" id="node-4214327--21489018797" data-pisa="biorxiv;2024.11.11.622837v1" data-pisa-master="biorxiv;2024.11.11.622837" data-apath="/biorxiv/early/2024/11/11/2024.11.11.622837.atom" data-hw-author-tooltip-instance="highwire_author_tooltip"><div class="highwire-cite highwire-cite-highwire-article highwire-citation-biorxiv-article-top clearfix has-author-tooltip" > <span class="biorxiv-article-type"> New Results </span> <h1 class="highwire-cite-title" id="page-title">Elovl1 inhibition reduced very long chain fatty acids in a mouse model of adrenoleukodystrophy</h1> <div class="highwire-cite-authors" ><span class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0"><span class="nlm-given-names">Jeremy Y.</span> <span class="nlm-surname">Huang</span></span>, <span class="highwire-citation-author" data-delta="1"><span class="nlm-given-names">Brian</span> <span class="nlm-surname">Freed</span></span>, <span class="highwire-citation-author" data-delta="2"><span class="nlm-given-names">Martin</span> <span class="nlm-surname">Hanus</span></span>, <span class="highwire-citation-author" data-delta="3"><span class="nlm-given-names">Kelly</span> <span class="nlm-surname">Keefe</span></span>, <span class="highwire-citation-author" data-delta="4"><span class="nlm-given-names">Ming Sum Ruby</span> <span class="nlm-surname">Chiang</span></span>, <span class="highwire-citation-author" data-delta="5"><span class="nlm-given-names">Alexander</span> <span class="nlm-surname">Brezzani</span></span>, <span class="highwire-citation-author" data-delta="6"><span class="nlm-given-names">Yongyi</span> <span class="nlm-surname">Luo</span></span>, <span class="highwire-citation-author" data-delta="7"><span class="nlm-given-names">Yihang</span> <span class="nlm-surname">Li</span></span>, <span class="highwire-citation-author" data-delta="8"><span class="nlm-given-names">Becky</span> <span class="nlm-surname">Lam</span></span>, <span class="highwire-citation-author" data-delta="9"><span class="nlm-given-names">Stephanie</span> <span class="nlm-surname">Holley</span></span>, <span class="highwire-citation-author" data-delta="10"><span class="nlm-given-names">Joseph</span> <span class="nlm-surname">Gans</span></span>, <span class="highwire-citation-author" data-delta="11"><span class="nlm-given-names">Zuzana</span> <span class="nlm-surname">Dostalova</span></span>, <span class="highwire-citation-author" data-delta="12"><span class="nlm-given-names">Buyun</span> <span class="nlm-surname">Tang</span></span>, <span class="highwire-citation-author" data-delta="13"><span class="nlm-given-names">Clifford</span> <span class="nlm-surname">Phaneuf</span></span>, <span class="highwire-citation-author" data-delta="14"><span class="nlm-given-names">Erin</span> <span class="nlm-surname">Teeple</span></span>, <span class="highwire-citation-author" data-delta="15"><span class="nlm-given-names">Laura</span> <span class="nlm-surname">Parisi</span></span>, <span class="highwire-citation-author" data-delta="16"><span class="nlm-given-names">Lilu</span> <span class="nlm-surname">Guo</span></span>, <span class="highwire-citation-author" data-delta="17"><span class="nlm-given-names">Zhonglin</span> <span class="nlm-surname">Zhao</span></span>, <span class="highwire-citation-author" data-delta="18"><span class="nlm-given-names">Sofia N.</span> <span class="nlm-surname">Kinton</span></span>, <span class="highwire-citation-author" data-delta="19"><span class="nlm-given-names">Jacquelyn</span> <span class="nlm-surname">Dwyer</span></span>, <span class="highwire-citation-author" data-delta="20"><span class="nlm-given-names">Sandrine</span> <span class="nlm-surname">Teixeira</span></span>, <span class="highwire-citation-author" data-delta="21"><span class="nlm-given-names">Hong</span> <span class="nlm-surname">Ma</span></span>, <span class="highwire-citation-author" data-delta="22"><span class="nlm-given-names">Gary</span> <span class="nlm-surname">Asmussen</span></span>, <span class="highwire-citation-author" data-delta="23"><span class="nlm-given-names">Rajashree</span> <span class="nlm-surname">McLaren</span></span>, <span class="highwire-citation-author" data-delta="24"><span class="nlm-given-names">Donghui</span> <span class="nlm-surname">Wang</span></span>, <span class="highwire-citation-author" data-delta="25"><span class="nlm-given-names">Ann</span> <span class="nlm-surname">Baker</span></span>, <span class="highwire-citation-author" data-delta="26"><span class="nlm-given-names">Craig S.</span> <span class="nlm-surname">Siegel</span></span>, <span class="highwire-citation-author" data-delta="27"><span class="nlm-given-names">David</span> <span class="nlm-surname">Fink</span></span>, <span class="highwire-citation-author" data-delta="28"><span class="nlm-given-names">Kristen</span> <span class="nlm-surname">Randall</span></span>, <span class="highwire-citation-author" data-delta="29"><span class="nlm-given-names">Alexei</span> <span class="nlm-surname">Belenky</span></span>, <span class="highwire-citation-author" data-delta="30"><span class="nlm-given-names">Suchitra</span> <span class="nlm-surname">Venugopal</span></span>, <span class="highwire-citation-author" data-delta="31"><span class="nlm-given-names">Giorgio</span> <span class="nlm-surname">Gaglia</span></span>, <span class="highwire-citation-author" data-delta="32"><span class="nlm-given-names">Jennifer</span> <span class="nlm-surname">Johnson</span></span>, <span class="highwire-citation-author" data-delta="33"><span class="nlm-given-names">Dinesh S.</span> <span class="nlm-surname">Bangari</span></span>, <span class="highwire-citation-author" data-delta="34"><span class="nlm-given-names">S. Pablo</span> <span class="nlm-surname">Sardi</span></span>, <span class="highwire-citation-author" data-delta="35"><span class="nlm-given-names">Bailin</span> <span class="nlm-surname">Zhang</span></span>, <span class="highwire-citation-author" data-delta="36"><span class="nlm-given-names">Alexander</span> <span class="nlm-surname">Michel</span></span>, <span class="highwire-citation-author" data-delta="37"><span class="nlm-given-names">Jonathan D.</span> <span class="nlm-surname">Proto</span></span>, <span class="highwire-citation-author" data-delta="38"><span class="nlm-given-names">Alla</span> <span class="nlm-surname">Kloss</span></span>, <span class="highwire-citation-author" data-delta="39"><span class="nlm-given-names">Tatiana</span> <span class="nlm-surname">Gladysheva</span></span>, <span class="highwire-citation-author" data-delta="40"><span class="nlm-given-names">Can</span> <span class="nlm-surname">Kayatekin</span></span></span></div> <div class="highwire-cite-metadata" ><span class="highwire-cite-metadata-doi highwire-cite-metadata"><span class="label">doi:</span> https://doi.org/10.1101/2024.11.11.622837 </span></div> </div> <div id="hw-article-author-popups-node-4214327--21489018797" style="display: none;"><div class="author-tooltip-0"><div class="author-tooltip-name">Jeremy Y. 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id="abstract-1"><h2>Abstract</h2><p id="p-2">Adrenoleukodystrophy (ALD) is a rare neurometabolic disease caused by mutations in the <em>ABCD1</em> gene, which encodes for the peroxisomal very long chain fatty acid (VLCFAs) transporter. It is a debilitating disorder, which has a spectrum of clinical presentations. The most severe form is a rapidly progressing demyelinating disease called cerebral ALD or CALD. Patients with cALD have a life expectancy of 2-4 years after onset and symptoms often manifest in childhood. The other forms are adrenomyeloneuropathy or AMN, which is a slower progressing degeneration of the spinal cord, and adrenal insufficiency (Addison disease). Since the accumulation of VLCFAs are a common factor in all ALD pathologies, we identified therapeutic approach that could correct this metabolic defect. We developed a substrate reduction therapy (SRT) for ALD in the form of an inhibitor of the lipid elongase principally responsible for the generation of VLCFAs, Elovl1. This small molecule was able to successfully reduce the accumulation of VLCFA in the brain and spinal cord of <em>ABCD1</em><sup>−/y</sup> mice. We used single nuclei RNA seq to identify the pathways altered in the <em>ABCD1</em><sup>−/y</sup> mouse and corrected with Elovl1 inhibition. Though many lipid metabolism genes and pathways were indeed corrected, treatment with the Elovl1 inhibitor unexpectedly led to profound transcriptional changes beyond correction of pathways altered by loss of <em>ABCD1</em>. These data suggest that Elovl1 inhibition may have broader consequences in <em>ABCD1</em><sup>−/y</sup> mice than correction of lipid homeostasis.</p></div><h3>Competing Interest Statement</h3><p id="p-3">All authors are Sanofi employees or were Sanofi employees when they contributed to this project</p><span class="highwire-journal-article-marker-end"></span></div><span class="related-urls"></span></div></div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-biorxiv-copyright" > <div class="pane-content"> <div class="field field-name-field-highwire-copyright field-type-text field-label-inline clearfix"><div class="field-label">Copyright </div><div class="field-items"><div class="field-item even">The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.<span class="license-type"> It is made available under a <a href="http://creativecommons.org/licenses/by-nc-nd/4.0/" class="" 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><span class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0"><span class="nlm-given-names">Jeremy Y.</span> <span class="nlm-surname">Huang</span></span>, <span class="highwire-citation-author" data-delta="1"><span class="nlm-given-names">Brian</span> <span class="nlm-surname">Freed</span></span>, <span class="highwire-citation-author" data-delta="2"><span class="nlm-given-names">Martin</span> <span class="nlm-surname">Hanus</span></span>, <span class="highwire-citation-author" data-delta="3"><span class="nlm-given-names">Kelly</span> <span class="nlm-surname">Keefe</span></span>, <span class="highwire-citation-author" data-delta="4"><span class="nlm-given-names">Ming Sum Ruby</span> <span class="nlm-surname">Chiang</span></span>, <span class="highwire-citation-author" data-delta="5"><span class="nlm-given-names">Alexander</span> <span class="nlm-surname">Brezzani</span></span>, <span class="highwire-citation-author" data-delta="6"><span class="nlm-given-names">Yongyi</span> <span class="nlm-surname">Luo</span></span>, <span class="highwire-citation-author" data-delta="7"><span class="nlm-given-names">Yihang</span> <span class="nlm-surname">Li</span></span>, <span class="highwire-citation-author" data-delta="8"><span class="nlm-given-names">Becky</span> <span class="nlm-surname">Lam</span></span>, <span class="highwire-citation-author" data-delta="9"><span class="nlm-given-names">Stephanie</span> <span class="nlm-surname">Holley</span></span>, <span class="highwire-citation-author" data-delta="10"><span class="nlm-given-names">Joseph</span> <span class="nlm-surname">Gans</span></span>, <span class="highwire-citation-author" data-delta="11"><span class="nlm-given-names">Zuzana</span> <span class="nlm-surname">Dostalova</span></span>, <span class="highwire-citation-author" data-delta="12"><span class="nlm-given-names">Buyun</span> <span class="nlm-surname">Tang</span></span>, <span class="highwire-citation-author" 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><span class="highwire-cite-metadata-journal highwire-cite-metadata">bioRxiv </span><span class="highwire-cite-metadata-pages highwire-cite-metadata">2024.11.11.622837; </span><span class="highwire-cite-metadata-doi highwire-cite-metadata"><span class="doi_label">doi:</span> https://doi.org/10.1101/2024.11.11.622837 </span></div> </div> </div> </div> <div class="highwire-citation-formats"> <h2>Citation Manager Formats</h2> <div class="highwire-citation-formats-links"> <span class="Z3988" 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