{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:56:00Z","timestamp":1760237760264,"version":"build-2065373602"},"reference-count":34,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,6,25]],"date-time":"2020-06-25T00:00:00Z","timestamp":1593043200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["2R01 NS044146-05A1"],"award-info":[{"award-number":["2R01 NS044146-05A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1086311 and 1144791"],"award-info":[{"award-number":["1086311 and 1144791"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005202","name":"Muscular Dystrophy Association","doi-asserted-by":"publisher","award":["4352"],"award-info":[{"award-number":["4352"]}],"id":[{"id":"10.13039\/100005202","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Duchenne muscular dystrophy (DMD) is a severe muscle wasting disease typically caused by protein-truncating mutations that preclude synthesis of a functional dystrophin. Exonic deletions are the most common type of DMD lesion, however, whole exon duplications account for between 10\u201315% of all reported mutations. Here, we describe in vitro evaluation of antisense oligonucleotide-induced splice switching strategies to re-frame the transcript disrupted by a multi-exon duplication within the DMD gene. Phosphorodiamidate morpholino oligomers and phosphorodiamidate morpholino oligomers coupled to a cell penetrating peptide were evaluated in a Duchenne muscular dystrophy patient cell strain carrying an exon 14\u201317 duplication. Two strategies were employed; the conventional approach was to remove both copies of exon 17 in addition to exon 18, and the second strategy was to remove only the first copy of exon 17. Both approaches result in a larger than normal but in-frame DMD transcript, but surprisingly, the removal of only the first exon 17 appeared to be more efficient in restoring dystrophin, as determined using western blotting. The emergence of a normal sized DMD mRNA transcript that was not apparent in untreated samples may have arisen from back splicing and could also account for some of the dystrophin protein being produced.<\/jats:p>","DOI":"10.3390\/ijms21124511","type":"journal-article","created":{"date-parts":[[2020,6,25]],"date-time":"2020-06-25T10:36:54Z","timestamp":1593081414000},"page":"4511","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Single Exon Skipping Can Address a Multi-Exon Duplication in the Dystrophin Gene"],"prefix":"10.3390","volume":"21","author":[{"given":"Kane","family":"Greer","sequence":"first","affiliation":[{"name":"Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Murdoch 6150, Australia"},{"name":"Perron Institute for Neurological and Translational Science, Perth 6009, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Russell","family":"Johnsen","sequence":"additional","affiliation":[{"name":"Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Murdoch 6150, Australia"},{"name":"Perron Institute for Neurological and Translational Science, Perth 6009, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoram","family":"Nevo","sequence":"additional","affiliation":[{"name":"Institute of Neurology, Schneider Children\u2019s Medical Center of Israel, Tel-Aviv University,\r\nTel-Aviv 62919, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yakov","family":"Fellig","sequence":"additional","affiliation":[{"name":"Pathology Department, Hadassah-Hebrew-University Medical Center, Jerusalem 91120, Israel;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8632-641X","authenticated-orcid":false,"given":"Susan","family":"Fletcher","sequence":"additional","affiliation":[{"name":"Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Murdoch 6150, Australia"},{"name":"Perron Institute for Neurological and Translational Science, Perth 6009, Australia"},{"name":"Centre for Neuromuscular & Neurological Disorders, University of Western Australia, Perth 6009, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steve D.","family":"Wilton","sequence":"additional","affiliation":[{"name":"Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Murdoch 6150, Australia"},{"name":"Perron Institute for Neurological and Translational Science, Perth 6009, Australia"},{"name":"Centre for Neuromuscular & Neurological Disorders, University of Western Australia, Perth 6009, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1002\/ana.23528","article-title":"Evidence-based path to newborn screening for Duchenne muscular dystrophy","volume":"71","author":"Mendell","year":"2012","journal-title":"Ann. 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