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Repair Drive involves transient conditioning of the liver by knocking down an essential gene,\n            <jats:italic>fumarylacetoacetate hydrolase<\/jats:italic>\n            (\n            <jats:italic>Fah<\/jats:italic>\n            ), and delivering an untargetable version of the essential gene in cis with a therapeutic transgene. We show that Repair Drive increased the percentage of correctly targeted hepatocytes in healthy wild-type mice up to 25%, which resulted in a fivefold increased expression of a therapeutic transgene,\n            <jats:italic>human factor IX<\/jats:italic>\n            (\n            <jats:italic>FIX<\/jats:italic>\n            ). Repair Drive was well tolerated and did not induce toxicity or tumorigenesis during a 1-year follow-up. This approach may broaden the range of liver diseases that can be treated with somatic genome editing.\n          <\/jats:p>","DOI":"10.1126\/scitranslmed.adk3920","type":"journal-article","created":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T18:59:31Z","timestamp":1739386771000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":7,"title":["In vivo expansion of gene-targeted hepatocytes through transient inhibition of an essential gene"],"prefix":"10.1126","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9823-1397","authenticated-orcid":true,"given":"Marco","family":"De Giorgi","sequence":"first","affiliation":[{"name":"Department of Integrative Physiology, Baylor College of Medicine, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3599-1687","authenticated-orcid":true,"given":"So Hyun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Rice University, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Castoreno","sequence":"additional","affiliation":[{"name":"Alnylam Pharmaceuticals Inc., Cambridge, MA 02142, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4234-1175","authenticated-orcid":true,"given":"Mingming","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Rice University, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8697-8610","authenticated-orcid":true,"given":"Ayrea","family":"Hurley","sequence":"additional","affiliation":[{"name":"Department of Integrative Physiology, Baylor College of Medicine, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6083-4013","authenticated-orcid":true,"given":"Lavanya","family":"Saxena","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Rice University, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1840-0948","authenticated-orcid":true,"given":"Marcel A.","family":"Chuecos","sequence":"additional","affiliation":[{"name":"Department of Integrative Physiology, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Translational Biology and Molecular Medicine Program, Baylor College of Medicine, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1471-0447","authenticated-orcid":true,"given":"Christopher J.","family":"Walkey","sequence":"additional","affiliation":[{"name":"Department of Integrative Physiology, Baylor College of Medicine, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2297-6103","authenticated-orcid":true,"given":"Alexandria M.","family":"Doerfler","sequence":"additional","affiliation":[{"name":"Department of Integrative Physiology, Baylor College of Medicine, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7363-0938","authenticated-orcid":true,"given":"Mia N.","family":"Furgurson","sequence":"additional","affiliation":[{"name":"Department of Integrative Physiology, Baylor College of Medicine, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0544-878X","authenticated-orcid":true,"given":"M. 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