{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:10:35Z","timestamp":1768507835746,"version":"3.49.0"},"posted":{"date-parts":[[2023,7,29]]},"group-title":"Genetics","reference-count":55,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,7,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Homology Directed Repair (HDR)-based genome editing is an approach that could permanently correct a broad range of genetic diseases. However, its utility is limited by inefficient and imprecise DNA repair mechanisms in terminally differentiated tissues. Here, we tested \u201cRepair Drive\u201d, a novel method for improving targeted gene insertion in the liver by selectively expanding correctly repaired hepatocytes\n                  <jats:italic>in vivo<\/jats:italic>\n                  . Our system consists of transient conditioning of the liver by knocking down an essential gene, and delivery of an untargetable version of the essential gene\n                  <jats:italic>in cis<\/jats:italic>\n                  with a therapeutic transgene. We show that Repair Drive dramatically increases the percentage of correctly targeted hepatocytes, up to 25%. This resulted in a five-fold increased expression of a therapeutic transgene. Repair Drive was well-tolerated and did not induce toxicity or tumorigenesis in long term follow up. This approach will broaden the range of liver diseases that can be treated with somatic genome editing.\n                <\/jats:p>","DOI":"10.1101\/2023.07.26.550728","type":"posted-content","created":{"date-parts":[[2023,7,29]],"date-time":"2023-07-29T12:45:25Z","timestamp":1690634725000},"source":"Crossref","is-referenced-by-count":2,"title":["<i>In vivo<\/i>\n                  expansion of gene-targeted hepatocytes through transient inhibition of an essential gene"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9823-1397","authenticated-orcid":false,"given":"Marco","family":"De Giorgi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"So Hyun","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Castoreno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingming","family":"Cao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayrea","family":"Hurley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lavanya","family":"Saxena","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcel A.","family":"Chuecos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher J.","family":"Walkey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandria M.","family":"Doerfler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mia N.","family":"Furgurson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. 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