{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T07:50:24Z","timestamp":1775980224084,"version":"3.50.1"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T00:00:00Z","timestamp":1736467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T00:00:00Z","timestamp":1736467200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS\u201090634"],"award-info":[{"award-number":["NS\u201090634"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AR\u201070517"],"award-info":[{"award-number":["AR\u201070517"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI\u2010177600"],"award-info":[{"award-number":["AI\u2010177600"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS\u2010131416"],"award-info":[{"award-number":["NS\u2010131416"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Adeno\u2010associated virus (AAV) 8 and 9 are in clinical trials for treating neuromuscular diseases such as Duchenne muscular dystrophy (DMD). Muscle consists of myofibres of different types and sizes. However, little is known about the fibre type and fibre size tropism of AAV in large mammals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We evaluated fibre type\u2010 and size\u2010specific transduction properties of AAV8 and AAV9 in 17 dogs that received systemic gene transfer (dose 1.94\u2009\u00b1\u20090.52\u2009\u00d7\u200910\n                      <jats:sup>14<\/jats:sup>\n                      \u2009vg\/kg; injected at 2.86\u2009\u00b1\u20090.30\u2009months; harvested at 20.79\u2009\u00b1\u20093.30\u2009months). For AAV8, two DMD dogs and three carrier dogs received an alkaline phosphatase (AP) reporter vector, and five DMD dogs received a four\u2010repeat microdystrophin (uDys) vector. For AAV9, one normal and one DMD dog received the AP vector, and five DMD dogs received a five\u2010repeat uDys vector. Association between AAV transduction and the fibre type\/size was studied in three muscles that showed mosaic transgene expression, including the biceps femoris, teres major and latissimus dorsi.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Transgene expression was detected in 30%\u201345% of myofibres. In the AP reporter vector\u2013injected dogs, neither AAV8 nor AAV9 showed a statistically significant fibre type preference. Interestingly, AP expression was enriched in smaller fibres. In uDys\u2010treated DMD dogs, slow and fast myofibres were equally transduced. Notably, uDys\u2010expressing myofibres were significantly larger than uDys\u2010negative myofibres irrespective of the AAV serotype (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). In AAV8 uDys vector\u2013injected dogs, the mini\u2010Feret diameter was 15%, 16% and 23% larger in uDys\u2010positive slow, fast and hybrid fibres, respectively; the cross\u2010sectional area was 30%, 34% and 46% larger in uDys\u2010positive slow, fast and hybrid fibres, respectively. In AAV9 uDys vector\u2013injected dogs, the mini\u2010Feret diameter was 12%, 13% and 25% larger in uDys\u2010positive slow, fast and hybrid fibres, respectively; the cross\u2010sectional area was 25%, 28% and 59% larger in uDys\u2010positive slow, fast and hybrid fibres, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our studies suggest that AAV8 and AAV9 transduce fast and slow myofibres at equivalent efficiency. Importantly, uDys therapy effectively prevented dystrophic myofibre atrophy. Our study provides important insight into systemic muscle AAV delivery in large mammals and supports further development of uDys gene therapy for DMD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.13681","type":"journal-article","created":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T03:45:37Z","timestamp":1736480737000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Adeno\u2010Associated Virus 8 and 9 Myofibre Type\/Size Tropism Profiling Reveals Therapeutic Effect of Microdystrophin in Canines"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9112-5452","authenticated-orcid":false,"given":"Matthew\u00a0J.","family":"Burke","sequence":"first","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, School of Medicine University of Missouri  Columbia Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Braiden\u00a0M.","family":"Blatt","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, School of Medicine University of Missouri  Columbia Missouri USA"},{"name":"College of Veterinary Medicine University of Missouri  Columbia Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James\u00a0A.","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, School of Medicine University of Missouri  Columbia Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dennis\u00a0O.","family":"P\u00e9rez\u2010L\u00f3pez","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, School of Medicine University of Missouri  Columbia Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongping","family":"Yue","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, School of Medicine University of Missouri  Columbia Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiufang","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, School of Medicine University of Missouri  Columbia Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chady\u00a0H.","family":"Hakim","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, School of Medicine University of Missouri  Columbia Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gang","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biomedical Engineering, College of Engineering University of Missouri  Columbia Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roland\u00a0W.","family":"Herzog","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Herman B Wells Center for Pediatric Research Indiana University  Indianapolis Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4109-1132","authenticated-orcid":false,"given":"Dongsheng","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, School of Medicine University of Missouri  Columbia Missouri USA"},{"name":"Department of Chemical and Biomedical Engineering, College of Engineering University of Missouri  Columbia Missouri USA"},{"name":"Department of Biomedical Sciences, College of Veterinary Medicine University of Missouri  Columbia Missouri USA"},{"name":"Department of Neurology, School of Medicine University of Missouri  Columbia Missouri 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