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Patients diagnosed with CBS deficiency are currently treated by a combination of vitamin supplementation and restriction of foods containing the homocysteine precursor methionine, but the effectiveness of this therapy is limited due to poor compliance. A mouse model for CBS deficiency (<jats:italic>Tg\u2010I278T Cbs<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup><jats:italic>)<\/jats:italic> was used to evaluate a potential gene therapy approach to treat CBS deficiency utilizing an AAVrh.10\u2010based vector containing the human <jats:italic>CBS<\/jats:italic> cDNA downstream of the constitutive, strong CAG promoter (AAVrh.10hCBS). Mice were administered a single dose of virus and followed for up to 1 year. The data demonstrated a dose\u2010dependent increase in liver CBS activity and a dose\u2010dependent decrease in serum tHcy. Liver CBS enzyme activity at 1 year was similar to <jats:italic>Cbs<\/jats:italic><jats:sup><jats:italic>+\/\u2212<\/jats:italic><\/jats:sup> control mice. Mice given the highest dose (5.6\u2009\u00d7\u200910<jats:sup>11<\/jats:sup> genomes\/mouse) had mean serum tHcy decrease of 97% 1 week after injection and an 81% reduction 1 year after injection. Treated mice had either full\u2010 or substantial correction of alopecia, bone loss, and fat mass phenotypes associated with <jats:italic>Cbs<\/jats:italic> deficiency in mice. Our findings show that AAVrh.10\u2010based gene therapy is highly effective in treating CBS deficiency in mice and supports additional pre\u2010clinical testing for eventual use human trials.<\/jats:p>","DOI":"10.1002\/jimd.12437","type":"journal-article","created":{"date-parts":[[2021,9,16]],"date-time":"2021-09-16T10:06:05Z","timestamp":1631786765000},"page":"1382-1392","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Long\u2010term functional correction of cystathionine \u03b2\u2010synthase deficiency in mice by adeno\u2010associated viral gene therapy"],"prefix":"10.1002","volume":"44","author":[{"given":"Hyung\u2010Ok","family":"Lee","sequence":"first","affiliation":[{"name":"Cancer Biology Program Fox Chase Cancer Center  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiana O.","family":"Salami","sequence":"additional","affiliation":[{"name":"Department of 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