{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T06:29:12Z","timestamp":1777703352635,"version":"3.51.4"},"reference-count":37,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,6,29]],"date-time":"2025-06-29T00:00:00Z","timestamp":1751155200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science and Technology Council","award":["106-2320-B-075-003-MY3"],"award-info":[{"award-number":["106-2320-B-075-003-MY3"]}]},{"name":"National Science and Technology Council","award":["110-2314-B-075-018-MY3"],"award-info":[{"award-number":["110-2314-B-075-018-MY3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations in the GLA gene, resulting in \u03b1-galactosidase A (\u03b1-Gal A) deficiency and progressive accumulation of globotriaosylceramide (Gb3). Current therapies, such as enzyme replacement and chaperone therapy, have limitations, including incomplete biodistribution and mutation-specific efficacy. Gene therapy using adeno-associated virus (AAV) vectors presents a promising alternative. Methods: In this study, we assessed the dose-dependent effects of AAV8 and AAV9 vectors encoding human GLA in Gla knockout (Gla\u2212\/y) mice by measuring \u03b1-Gal A activity and monitoring safety. To evaluate therapeutic efficacy, symptomatic Fabry mice (G3STg\/+Gla\u2212\/y) were used. Results: AAV9-GLA produced significantly higher and more sustained enzyme activity than AAV8-GLA across plasma, liver, heart, and kidney. In symptomatic mice, AAV9-GLA achieved superior reductions in serum Gb3 and lyso-Gb3 levels, greater Gb3 clearance in heart and kidney tissues, and improved proteinuria. Anti-GLA IgG titers remained below threshold for the first four weeks and increased modestly by week eight, indicating a limited humoral immune response. No significant clinical signs or weight loss were observed in Gla\u2212\/y mice over the 3.5-month study period, supporting the favorable safety profile of AAV-mediated gene therapy. Conclusions: These findings demonstrate that AAV9 provides enhanced biodistribution and therapeutic efficacy compared to AAV8, supporting its potential for the treatment of Fabry disease.<\/jats:p>","DOI":"10.3390\/genes16070766","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T10:45:08Z","timestamp":1751366708000},"page":"766","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Comparative Evaluation of AAV8 and AAV9 Gene Therapy in Fabry Knockout (Gla\u2212\/y) and Symptomatic (G3STg\/+Gla\u2212\/y) Murine Models"],"prefix":"10.3390","volume":"16","author":[{"given":"Fu-Pang","family":"Chang","sequence":"first","affiliation":[{"name":"Institute of Clinical Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan"},{"name":"Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei 11227, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ya-Ting","family":"Lee","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pao-Hsung","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pei-Sin","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7410-0624","authenticated-orcid":false,"given":"Yun-Ru","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Taipei Veterans General Hospital, Taipei 11217, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3962-1739","authenticated-orcid":false,"given":"Dau-Ming","family":"Niu","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan"},{"name":"Department of Pediatrics, Taipei Veterans General Hospital, Taipei 11217, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/1750-1172-5-30","article-title":"Fabry disease","volume":"5","author":"Germain","year":"2010","journal-title":"Orphanet J. 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PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0304415"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/7\/766\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:01:24Z","timestamp":1760032884000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/7\/766"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,29]]},"references-count":37,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["genes16070766"],"URL":"https:\/\/doi.org\/10.3390\/genes16070766","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,29]]}}}