{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T11:00:26Z","timestamp":1790161226066,"version":"4.1.0"},"reference-count":70,"publisher":"SAGE Publications","issue":"1-2","license":[{"start":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:00:00Z","timestamp":1760572800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100009358","name":"Duchenne Research Fund","doi-asserted-by":"crossref","award":["P0171744"],"award-info":[{"award-number":["P0171744"]}],"id":[{"id":"10.13039\/100009358","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Human Gene Therapy"],"published-print":{"date-parts":[[2026,1,1]]},"abstract":"<jats:p>\n                    Significant progress has been made in gene therapy for Duchenne muscular dystrophy (DMD), a severe genetic disorder primarily affecting pediatric patients. However, the immune responses triggered by high-dose systemic delivery of adeno-associated virus (AAV) vectors remain a major challenge. These responses include the generation of long-lasting anti-capsid antibodies and potential immunity against the therapeutic transgene, rendering gene therapy ineffective. In addition, pre-existing anti-AAV antibodies exclude patients from eligibility for treatment. To address these limitations, we have developed an immunosuppression (IMS) strategy aimed at mitigating immune responses to the AAV capsid while enhancing microdystrophin expression. Using an optimized expression cassette (AAV9-UF\u00b5Dys1) for sustained microdystrophin expression in striated muscle and heart, we observed a 40% improvement in muscle force compared with animals receiving a GFP-encoding control AAV9 vector. In\n                    <jats:italic toggle=\"yes\">mdx<\/jats:italic>\n                    mice, a single-dose IMS regimen significantly increased microdystrophin expression in cardiac and skeletal tissues and repeat dosing further enhanced expression, an effect not observed in non-IMS-treated\n                    <jats:italic toggle=\"yes\">mdx<\/jats:italic>\n                    mice. To model pre-existing immunity, we immune-challenged wild-type mice with empty AAV9 capsids and tracked antibody responses over time. The IMS regimen effectively reduced total anti-AAV antibody levels and increased microdystrophin expression in UF\u00b5Dys1-treated mice. These findings highlight the potential of IMS to minimize immune barriers, facilitate repeat AAV administration, and expand the therapeutic window for DMD gene therapy. Our results support the further development of AAV-mediated approaches using either microdystrophin-expressing vectors or next-generation systems delivering full-length or near-full-length dystrophin.\n                  <\/jats:p>","DOI":"10.1177\/10430342251385586","type":"journal-article","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T10:37:17Z","timestamp":1760611037000},"page":"17-32","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Enhancing AAV9-UF\u03bcDys1 Gene Therapy Efficacy Through Immunosuppression in Mice with Pre-Existing Immunity and Enabling Redosing Strategies for Duchenne Muscular Dystrophy"],"prefix":"10.1177","volume":"37","author":[{"given":"Madhurima","family":"Saha","sequence":"first","affiliation":[{"name":"Department of Pediatrics, College of Medicine, University of Florida, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radhika","family":"Bhake","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, College of Medicine, University of Florida, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig A.","family":"Meyers","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, College of Medicine, University of Florida, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten","family":"Coleman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, College of Medicine, University of Florida, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prasad D.","family":"Trivedi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, College of Medicine, University of Florida, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitch","family":"Gallman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, College of Medicine, University of Florida, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moanaro","family":"Biswas","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, School of Medicine, Indiana University, Indianapolis, Indiana, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland W.","family":"Herzog","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, School of Medicine, Indiana University, Indianapolis, Indiana, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry J.","family":"Byrne","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, College of Medicine, University of Florida, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Corti","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, College of Medicine, University of Florida, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,10,16]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-01-306647"},{"key":"e_1_3_5_3_2","article-title":"Thrombotic Microangiopathy Following Systemic AAV Administration is Dependent on Anti-Capsid Antibodies","author":"Salabarria S","year":"2023","unstructured":"Salabarria S, , Corti M, , Coleman KE, et al. Thrombotic Microangiopathy Following Systemic AAV Administration is Dependent on Anti-Capsid Antibodies. J Clin Invest, 2023.","journal-title":"J Clin Invest"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00487-6"},{"key":"e_1_3_5_5_2","article-title":"Duchenne Muscular Dystrophy","author":"Iannaccone ST","year":"2021","unstructured":"Iannaccone ST, , Nanjiani Z. Duchenne Muscular Dystrophy. Nat Rev Dis Primers, 2021.","journal-title":"Nat Rev Dis Primers"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2024.1360224"},{"key":"e_1_3_5_7_2","article-title":"Gene Therapy for DMD","author":"Treat-NMD","year":"2023","unstructured":"Treat-NMD. Gene Therapy for DMD. 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