{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T21:21:35Z","timestamp":1777670495290,"version":"3.51.4"},"reference-count":73,"publisher":"SAGE Publications","issue":"9-10","license":[{"start":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T00:00:00Z","timestamp":1682899200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Human Gene Therapy"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:p>\n                    Adeno-associated virus (AAV)-mediated systemic micro-dystrophin (\u03bcDys) therapy is currently in clinical trials. The hope is to permanently improve the life quality of Duchenne muscular dystrophy (DMD) patients. Numerous preclinical studies have been conducted to support these trials. However, none examined whether a single therapy at a young age can lead to lifelong disease amelioration. To address this critical question, we injected 1\u2009\u00d7\u200910\n                    <jats:sup>13<\/jats:sup>\n                    vg particles\/mouse of an AAV serotype-9\u2009\u03bcDys vector to 3-month-old mdx mice through the tail vein. Therapeutic outcomes were evaluated at the age of 11 months (adulthood, 8 months postinjection) and 21 months (terminal age, 18 months postinjection). Immunostaining and Western blot showed saturated supraphysiological levels of \u03bcDys expression in skeletal muscle and heart till the end of the study. Treatment significantly improved grip force and treadmill running, and significantly reduced the serum creatine kinase level at both time points. Since cardiac death is a major threat in late-stage patients, we evaluated cardiac electrophysiology and hemodynamics by ECG and the closed-chest cardiac catheter assay, respectively. Significant improvements were observed in these assays. Importantly, many ECG and hemodynamic parameters (heart rate, PR interval, QRS duration, QTc interval, end-diastolic\/systolic volume, dP\/dt max and min, max pressure, and ejection fraction) were completely normalized at 21 months of age. Our results have provided direct evidence that a single systemic AAV \u03bcDys therapy has the potential to provide lifelong benefits in the murine DMD model.\n                  <\/jats:p>","DOI":"10.1089\/hum.2022.181","type":"journal-article","created":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T05:45:32Z","timestamp":1670996732000},"page":"449-458","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":11,"title":["Lifelong Outcomes of Systemic Adeno-Associated Virus Micro-Dystrophin Gene Therapy in a Murine Duchenne Muscular Dystrophy Model"],"prefix":"10.1177","volume":"34","author":[{"given":"Nalinda B.","family":"Wasala","sequence":"first","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, School of Medicine, The 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, The University of Missouri, Columbia, Missouri, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bryan","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, School of Medicine, The University of Missouri, Columbia, Missouri, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5174-286X","authenticated-orcid":false,"given":"Jin-Hong","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, School of Medicine, The University of Missouri, Columbia, Missouri, USA"},{"name":"Department of Neurology, Pusan National University Yangsan Hospital, Yangsan, South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arun","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Division of Cellular and Molecular Therapy, Child Health Research Institute, Department of Pediatrics, Department of Molecular Genetics and Microbiology, The University of Florida College of Medicine, Gainesville, Florida, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gang","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biomedical Engineering, College of Engineering, The University of Missouri, Columbia, Missouri, 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, The University of Missouri, Columbia, Missouri, USA"},{"name":"Department of Chemical and Biomedical Engineering, College of Engineering, The University of Missouri, Columbia, Missouri, USA"},{"name":"Department of Neurology, School of Medicine, The University of Missouri, Columbia, Missouri, USA"},{"name":"Department of Biomedical Sciences, College of Veterinary Medicine, The University of Missouri, Columbia, Missouri, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2023,5,17]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2018.012"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-021-00248-3"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1086\/428143"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2016.07.006"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-019-0203-3"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1706198"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2004.09.011"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-019-0012-9"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-019-0205-4"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2009.256"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2013.210"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-8966(02)00078-0"},{"key":"e_1_3_5_14_2","first-page":"103","article-title":"From the smallest virus to the biggest gene: marching towards gene therapy for Duchenne muscular dystrophy","volume":"6","author":"Duan D","year":"2006","unstructured":"Duan D. 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Genethon announces first patient dosed in clinical trial of investigational gene therapy GNT 0004 for Duchenne muscular dystrophy. https:\/\/www.genethon.fr\/wp-content\/uploads\/2021\/04\/PR_GENETHON_DMD-1.pdf (last accessed April20 2021)."},{"key":"e_1_3_5_70_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddw210"},{"key":"e_1_3_5_71_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1211431109"},{"key":"e_1_3_5_72_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.064808"},{"key":"e_1_3_5_73_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-55704-8"},{"key":"e_1_3_5_74_2","doi-asserted-by":"publisher","DOI":"10.1089\/humc.2015.006"}],"container-title":["Human Gene Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/hum.2022.181","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/hum.2022.181","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/hum.2022.181","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T07:56:57Z","timestamp":1777449417000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/hum.2022.181"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5]]},"references-count":73,"journal-issue":{"issue":"9-10","published-print":{"date-parts":[[2023,5]]}},"alternative-id":["10.1089\/hum.2022.181"],"URL":"https:\/\/doi.org\/10.1089\/hum.2022.181","relation":{},"ISSN":["1043-0342","1557-7422"],"issn-type":[{"value":"1043-0342","type":"print"},{"value":"1557-7422","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5]]}}}