{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T22:35:02Z","timestamp":1784673302681,"version":"3.55.0"},"reference-count":152,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T00:00:00Z","timestamp":1732147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Patients suffering from an inherited severe liver disorder require lifelong treatment to prevent premature death. Until recently, the only curative treatment option was liver transplantation, which requires lifelong immune suppression. Now, liver-directed gene therapy, which is a much less invasive procedure, has become a market-approved treatment for hemophilia A and B. This may pave the way for it to become the treatment of choice for many other recessive inherited liver disorders with loss-of-function mutations. Inherited liver disease with toxic-gain-of-function or intrinsic hepatocyte damage may require alternative applications, such as integrating vectors or genome editing technologies, that can provide permanent or specific modification of the genome. We present an overview of currently available gene therapy strategies, i.e., gene supplementation, gene editing, and gene repair investigated in preclinical and clinical studies to treat inherited severe liver disorders. The advantages and limitations of these gene therapy applications are discussed in relation to the underlying disease mechanism.<\/jats:p>","DOI":"10.3390\/ijms252312514","type":"journal-article","created":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T12:25:42Z","timestamp":1732191942000},"page":"12514","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Gene Therapy for Inherited Liver Disease: To Add or to Edit"],"prefix":"10.3390","volume":"25","author":[{"given":"Yue","family":"Chen","sequence":"first","affiliation":[{"name":"Amsterdam University Medical Center, Tytgat Institute for Liver and Intestinal Research, AG&M, University of Amsterdam, Meibergdreef 69-71, 1105 BK Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9515-4103","authenticated-orcid":false,"given":"Niek P.","family":"van Til","sequence":"additional","affiliation":[{"name":"Amsterdam Leukodystrophy Center, Emma Children\u2019s Hospital, Amsterdam University Medical Center, Amsterdam Neuroscience, Cellular & Molecular Mechanisms, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands"},{"name":"Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8302-1672","authenticated-orcid":false,"given":"Piter J.","family":"Bosma","sequence":"additional","affiliation":[{"name":"Amsterdam University Medical Center, Tytgat Institute for Liver and Intestinal Research, AG&M, University of Amsterdam, Meibergdreef 69-71, 1105 BK Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1182\/hematology.2022000388","article-title":"Gene therapy for hemophilia","volume":"2022","author":"Nathwani","year":"2022","journal-title":"Hematol. 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