{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:27:52Z","timestamp":1787016472905,"version":"build-2736575974"},"reference-count":43,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"21","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2022,5,27]]},"abstract":"<jats:p>\n                    Muscular dystrophy is a progressive and ultimately lethal neuromuscular disease. Although gene editing and gene transfer hold great promise as therapies when administered before the onset of severe clinical symptoms, it is unclear whether these strategies can restore muscle function and improve survival in the late stages of muscular dystrophy.\n                    <jats:italic>\n                      Large\n                      <jats:sup>myd<\/jats:sup>\n                      \/Large\n                      <jats:sup>myd<\/jats:sup>\n                    <\/jats:italic>\n                    (\n                    <jats:italic>myd<\/jats:italic>\n                    ) mice lack expression of\n                    <jats:italic>like-acetylglucosaminyltransferase-1<\/jats:italic>\n                    (\n                    <jats:italic>Large1<\/jats:italic>\n                    ) and exhibit severe muscle pathophysiology, impaired mobility, and a markedly reduced life span. Here, we show that systemic delivery of AAV2\/9 CMV\n                    <jats:italic>Large1<\/jats:italic>\n                    (AAV\n                    <jats:italic>Large1<\/jats:italic>\n                    ) in &gt;34-week-old\n                    <jats:italic>myd<\/jats:italic>\n                    mice with advanced disease restores matriglycan expression on dystroglycan, attenuates skeletal muscle pathophysiology, improves motor and respiratory function, and normalizes systemic metabolism, which collectively and markedly extends survival. Our results in a mouse model of muscular dystrophy demonstrate that skeletal muscle function can be restored, illustrating its remarkable plasticity, and that survival can be greatly improved even after the onset of severe muscle pathophysiology.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.abn0379","type":"journal-article","created":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T13:57:46Z","timestamp":1653487066000},"source":"Crossref","is-referenced-by-count":18,"title":["<i>Large1<\/i>\n                    gene transfer in older\n                    <i>myd<\/i>\n                    mice with severe muscular dystrophy restores muscle function and greatly improves survival"],"prefix":"10.1126","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7663-5668","authenticated-orcid":true,"given":"Takahiro","family":"Yonekawa","sequence":"first","affiliation":[{"name":"Senator Paul D. Wellstone Muscular Dystrophy Specialized Research Center, Department of Molecular Physiology and Biophysics and Department of Neurology, Roy J. and Lucille A. Carver College of Medicine, Howard Hughes Medical Institute, The University of Iowa, Iowa City, IA 52242, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4101-0075","authenticated-orcid":true,"given":"Adam J.","family":"Rauckhorst","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology and Biophysics, Fraternal Order of Eagles Diabetes Research Center (FOEDRC), and FOEDRC Metabolomics Core Facility, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"El-Hattab","sequence":"additional","affiliation":[{"name":"Senator Paul D. Wellstone Muscular Dystrophy Specialized Research Center, Department of Molecular Physiology and Biophysics and Department of Neurology, Roy J. and Lucille A. Carver College of Medicine, Howard Hughes Medical Institute, The University of Iowa, Iowa City, IA 52242, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco A.","family":"Cuellar","sequence":"additional","affiliation":[{"name":"Senator Paul D. Wellstone Muscular Dystrophy Specialized Research Center, Department of Molecular Physiology and Biophysics and Department of Neurology, Roy J. and Lucille A. Carver College of Medicine, Howard Hughes Medical Institute, The University of Iowa, Iowa City, IA 52242, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8180-9562","authenticated-orcid":true,"given":"David","family":"Venzke","sequence":"additional","affiliation":[{"name":"Senator Paul D. Wellstone Muscular Dystrophy Specialized Research Center, Department of Molecular Physiology and Biophysics and Department of Neurology, Roy J. and Lucille A. Carver College of Medicine, Howard Hughes Medical Institute, The University of Iowa, Iowa City, IA 52242, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary E.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Senator Paul D. Wellstone Muscular Dystrophy Specialized Research Center, Department of Molecular Physiology and Biophysics and Department of Neurology, Roy J. and Lucille A. Carver College of Medicine, Howard Hughes Medical Institute, The University of Iowa, Iowa City, IA 52242, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2749-9855","authenticated-orcid":true,"given":"Hidehiko","family":"Okuma","sequence":"additional","affiliation":[{"name":"Senator Paul D. Wellstone Muscular Dystrophy Specialized Research Center, Department of Molecular Physiology and Biophysics and Department of Neurology, Roy J. and Lucille A. Carver College of Medicine, Howard Hughes Medical Institute, The University of Iowa, Iowa City, IA 52242, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvin D.","family":"Pewa","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology and Biophysics, Fraternal Order of Eagles Diabetes Research Center (FOEDRC), and FOEDRC Metabolomics Core Facility, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4549-6567","authenticated-orcid":true,"given":"Eric B.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology and Biophysics, Fraternal Order of Eagles Diabetes Research Center (FOEDRC), and FOEDRC Metabolomics Core Facility, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2066-5889","authenticated-orcid":true,"given":"Kevin P.","family":"Campbell","sequence":"additional","affiliation":[{"name":"Senator Paul D. Wellstone Muscular Dystrophy Specialized Research Center, Department of Molecular Physiology and Biophysics and Department of Neurology, Roy J. and Lucille A. 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