{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:52:16Z","timestamp":1785433936621,"version":"3.56.0"},"posted":{"date-parts":[[2026,5,10]]},"group-title":"Cell Biology","reference-count":51,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T00:00:00Z","timestamp":1778371200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"id":[{"id":"https:\/\/ror.org\/054f2wp19","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015326","name":"NIH Common Fund","doi-asserted-by":"crossref","award":["DP1 AG048917"],"award-info":[{"award-number":["DP1 AG048917"]}],"id":[{"id":"10.13039\/100015326","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Duchenne muscular dystrophy (DMD) is the most common, lethal X-linked neuromuscular disorder of childhood and is caused by mutations in the\n                  <jats:italic>Dmd<\/jats:italic>\n                  gene that disrupt dystrophin expression. Although adeno-associated virus-mediated gene therapies hold tremendous promise for DMD treatment, their clinical applications have been limited by dose-dependent vector and genome-level toxicities. Here, we developed and tested a single-vector adenine base editing strategy as a potentially safer genome editing approach to recode the pathogenic nonsense mutation into a benign missense mutation in\n                  <jats:italic>\n                    mdx\n                    <jats:sup>4cv<\/jats:sup>\n                  <\/jats:italic>\n                  DMD mouse model. Delivered using a muscle-tropic adeno-associated virus (MyoAAV) at a clinically-feasible dose (4E13 VG\/kg), this strategy enabled detectable molecular recoding of the\n                  <jats:italic>\n                    mdx\n                    <jats:sup>4cv<\/jats:sup>\n                  <\/jats:italic>\n                  mutation in mice ranging in age from 3 days to 6 months. Yet, the overall efficiency and therapeutic impact of\n                  <jats:italic>in vivo<\/jats:italic>\n                  base editing with this system was highest in mice treated at the juvenile stage, with animals administered MyoAAV vectors at 3 weeks of age showing robust recovery of dystrophin expression and significant improvement in muscle contractile properties only one month later. Notably, introduction of adenine base editors either earlier in development, in neonatal mice, or later, in adulthood, yielded substantially lower editing efficiencies, particularly in muscle satellite cells whose editing is essential to ensure durable rescue of dystrophin expression in growing and regenerating muscle. Taken together, these results demonstrate the therapeutic potential of single-vector adenine base editing for DMD and underscore the importance of recipient age and disease stage in achieving optimal treatment outcomes for this and other genetic muscle disorders.\n                <\/jats:p>","DOI":"10.64898\/2026.05.09.721064","type":"posted-content","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T05:10:16Z","timestamp":1778476216000},"source":"Crossref","is-referenced-by-count":0,"title":["<i>In vivo<\/i>\n                  base editing via single myotrophic adeno-associated viruses in dystrophic mouse muscle and satellite cells"],"prefix":"10.64898","author":[{"given":"Kuan-Hung","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Lam","sequence":"additional","affiliation":[{"name":"Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"van Ooijen","sequence":"additional","affiliation":[{"name":"Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeline","family":"Maier","sequence":"additional","affiliation":[{"name":"Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gracia","family":"Kassis","sequence":"additional","affiliation":[{"name":"Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regan","family":"Ellis","sequence":"additional","affiliation":[{"name":"Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Messemer","sequence":"additional","affiliation":[{"name":"Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Martin","sequence":"additional","affiliation":[{"name":"Myologica, LLC, New Market, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramzi","family":"Khairallah","sequence":"additional","affiliation":[{"name":"Myologica, LLC, New Market, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Wagers","sequence":"additional","affiliation":[{"name":"Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA"},{"name":"Harvard Medical School, Boston, MA"},{"name":"Section on Islet Cell and Regenerative Biology, Joslin Diabetes Center, Boston, MA"},{"name":"Harvard Stem Cell Institute, Cambridge, 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