{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:20:19Z","timestamp":1790688019220,"version":"4.1.0"},"reference-count":47,"publisher":"SAGE Publications","issue":"17-18","license":[{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"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":[[2021,9]]},"abstract":"<jats:p>\n                    Therapeutic exon skipping as a treatment for Duchenne muscular dystrophy (DMD) has largely concentrated on the delivery of antisense oligomers to treat out-of-frame exon deletions. Here we report on the preclinical development of an adeno-associated virus (AAV)-encapsidated viral vector containing four copies of the noncoding U7 small nuclear RNA (U7snRNA), each targeted to either the splice donor or the splice acceptor sites of\n                    <jats:italic toggle=\"yes\">DMD<\/jats:italic>\n                    exon 2. We have previously shown that delivery of this vector (scAAV9.U7.ACCA) to the Dup2 mouse model results in expression of full-length dystrophin from wild-type\n                    <jats:italic toggle=\"yes\">DMD<\/jats:italic>\n                    mRNA, as well as an internal ribosome entry site (IRES)-driven isoform translated only in the absence of exon 2 (deletion exon 2 [Del2] mRNA). Here we present the data from a rigorous dose escalation toxicity study in nonhuman primates, encompassing two doses (3\u2009\u00d7\u200910\n                    <jats:sup>13<\/jats:sup>\n                    and 8\u2009\u00d7\u200910\n                    <jats:sup>13<\/jats:sup>\n                    vg\/kg) and two time points (3 and 6 months postinjection). No evidence for significant toxicity was seen by biochemical, histopathologic, or clinical measures, providing evidence for safety that led to initiation of a first-in-human clinical trial.\n                  <\/jats:p>","DOI":"10.1089\/hum.2020.286","type":"journal-article","created":{"date-parts":[[2021,1,7]],"date-time":"2021-01-07T01:42:58Z","timestamp":1609983778000},"page":"882-894","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":42,"title":["Lack of Toxicity in Nonhuman Primates Receiving Clinically Relevant Doses of an AAV9.U7snRNA Vector Designed to Induce\n                    <i>DMD<\/i>\n                    Exon 2 Skipping"],"prefix":"10.1177","volume":"32","author":[{"given":"Liubov V.","family":"Gushchina","sequence":"first","affiliation":[{"name":"The Center for Gene Therapy, Abigail Wexner Research Institute, Nationwide Children's Hospital."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma C.","family":"Frair","sequence":"additional","affiliation":[{"name":"The Center for Gene Therapy, Abigail Wexner Research Institute, Nationwide Children's Hospital."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Rohan","sequence":"additional","affiliation":[{"name":"The Center for Gene Therapy, Abigail Wexner Research Institute, Nationwide Children's Hospital."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrienne J.","family":"Bradley","sequence":"additional","affiliation":[{"name":"The Center for Gene Therapy, Abigail Wexner Research Institute, Nationwide Children's Hospital."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tabatha R.","family":"Simmons","sequence":"additional","affiliation":[{"name":"The Center for Gene Therapy, Abigail Wexner Research Institute, Nationwide Children's Hospital."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hemantkumar D.","family":"Chavan","sequence":"additional","affiliation":[{"name":"Charles River Laboratories, Wilmington, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsin-Jung","family":"Chou","sequence":"additional","affiliation":[{"name":"Audentes Therapeutics, San Francisco, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Eggers","sequence":"additional","affiliation":[{"name":"Audentes Therapeutics, San Francisco, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan A.","family":"Waldrop","sequence":"additional","affiliation":[{"name":"The Center for Gene Therapy, Abigail Wexner Research Institute, Nationwide Children's Hospital."},{"name":"Departments of Pediatrics, The Ohio State University, Columbus, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Wein","sequence":"additional","affiliation":[{"name":"The Center for Gene Therapy, Abigail Wexner Research Institute, Nationwide Children's Hospital."},{"name":"Departments of Pediatrics, The Ohio State University, Columbus, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin M.","family":"Flanigan","sequence":"additional","affiliation":[{"name":"The Center for Gene Therapy, Abigail Wexner Research Institute, Nationwide Children's Hospital."},{"name":"Departments of Pediatrics, The Ohio State University, Columbus, Ohio, USA."},{"name":"Departments of Neurology, The Ohio State University, Columbus, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2021,9,23]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2020.107719"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.13.2415"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s000180300047"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-004-4190-0"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mt.6300200"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn382"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2016.152"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds082"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21114"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20367"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2015.08.005"},{"key":"e_1_3_6_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2009.08.010"},{"key":"e_1_3_6_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20913"},{"key":"e_1_3_6_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3628"},{"key":"e_1_3_6_16_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2010-0929"},{"key":"e_1_3_6_17_2","doi-asserted-by":"publisher","DOI":"10.1177\/0192623316663865"},{"key":"e_1_3_6_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/vcp.12272"},{"key":"e_1_3_6_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00580-017-2539-7"},{"key":"e_1_3_6_20_2","volume-title":"Background 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Chapter 1\u2014non-human primates: cynomolgus (Macaca fascicularis) and rhesus (Macaca mulatta) macaques and the common marmoset (Callithrix jacchus). In: McInnes EF, , Mann P, eds. Background Lesions in Laboratory Animals. Saint Louis: W.B. 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