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Affected patients have increased ornithine concentrations in blood and other body fluids and develop progressive constriction of vision fields leading to blindness. Current therapies are unsatisfactory and better treatments are highly needed. In two mouse models of OAT deficiency that recapitulates biochemical and retinal changes of GACR, we investigated the efficacy of an intravenously injected serotype 8 adeno\u2010associated (AAV8) vector expressing OAT under the control of a hepatocyte\u2010specific promoter. Following injections, OAT\u2010deficient mice showed reductions of ornithine concentrations in blood and eye cups compared with control mice injected with a vector expressing green fluorescent protein. AAV\u2010injected mice showed improved electroretinogram response and partial restoration of retinal structure up to one\u2010year post\u2010injection. In summary, hepatic OAT expression by AAV8 vector was effective at correction of hyperornithinemia and improved function and structure of the retina. In conclusion, this study provides proof\u2010of\u2010concept of efficacy of liver\u2010directed AAV\u2010mediated gene therapy of GACR.<\/jats:p>","DOI":"10.15252\/emmm.202217033","type":"journal-article","created":{"date-parts":[[2023,1,17]],"date-time":"2023-01-17T03:36:51Z","timestamp":1673926611000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Liver\u2010directed gene therapy for ornithine aminotransferase deficiency"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3281-0054","authenticated-orcid":false,"given":"Iolanda","family":"Boffa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Polishchuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"De Stefano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Dell'Aquila","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edoardo","family":"Nusco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Marrocco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2791-4526","authenticated-orcid":false,"given":"Matteo","family":"Audano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Pedretti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6035-8213","authenticated-orcid":false,"given":"Marianna","family":"Caterino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Bellezza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margherita","family":"Ruoppolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5000-3619","authenticated-orcid":false,"given":"Nico","family":"Mitro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5221-9288","authenticated-orcid":false,"given":"Barbara","family":"Cellini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0832-2472","authenticated-orcid":false,"given":"Alberto","family":"Auricchio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6895-8819","authenticated-orcid":false,"given":"Nicola","family":"Brunetti\u2010Pierri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,1,17]]},"reference":[{"key":"BFEMMM202217033_CR1","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1006\/exer.1999.0750","volume":"70","author":"A Ando","year":"2000","unstructured":"Ando A, Ueda M, Uyama M, Masu Y, Okumura T, Ito S (2000) Heterogeneity in ornithine cytotoxicity of bovine retinal pigment epithelial cells in primary culture. 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