{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:06:01Z","timestamp":1790251561720,"version":"4.1.0"},"reference-count":146,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2018,12,7]],"date-time":"2018-12-07T00:00:00Z","timestamp":1544140800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17H07142"],"award-info":[{"award-number":["17H07142"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18K14595"],"award-info":[{"award-number":["18K14595"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003806","name":"Hokuto Foundation for Bioscience","doi-asserted-by":"publisher","award":["H29No.8"],"award-info":[{"award-number":["H29No.8"]}],"id":[{"id":"10.13039\/501100003806","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Duchenne muscular dystrophy (DMD), a fatal X-linked recessive disorder, is caused mostly by frame-disrupting, out-of-frame deletions in the dystrophin (DMD) gene. Antisense oligonucleotide-mediated exon skipping is a promising therapy for DMD. Exon skipping aims to convert out-of-frame mRNA to in-frame mRNA and induce the production of internally-deleted dystrophin as seen in the less severe Becker muscular dystrophy. Currently, multiple exon skipping has gained special interest as a new therapeutic modality for this approach. Previous retrospective database studies represented a potential therapeutic application of multiple exon skipping. Since then, public DMD databases have become more useful with an increase in patient registration and advances in molecular diagnosis. Here, we provide an update on DMD genotype-phenotype associations using a global DMD database and further provide the rationale for multiple exon skipping development, particularly for exons 45\u201355 skipping and an emerging therapeutic concept, exons 3\u20139 skipping. Importantly, this review highlights the potential of multiple exon skipping for enabling the production of functionally-corrected dystrophin and for treating symptomatic patients not only with out-of-frame deletions but also those with in-frame deletions. We will also discuss prospects and challenges in multiple exon skipping therapy, referring to recent progress in antisense chemistry and design, as well as disease models.<\/jats:p>","DOI":"10.3390\/jpm8040041","type":"journal-article","created":{"date-parts":[[2018,12,10]],"date-time":"2018-12-10T03:36:41Z","timestamp":1544413001000},"page":"41","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":77,"title":["Multiple Exon Skipping in the Duchenne Muscular Dystrophy Hot Spots: Prospects and Challenges"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1573-4819","authenticated-orcid":false,"given":"Yusuke","family":"Echigoya","sequence":"first","affiliation":[{"name":"Laboratory of Biomedical Science, Department of Veterinary Medicine, Nihon University College of Bioresource Sciences, Fujisawa 252-0880, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5484-4183","authenticated-orcid":false,"given":"Kenji Rowel Q.","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G2H7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akinori","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Third Department of Medicine, Shinshu University School of Medicine, Matsumoto 390-8621, Japan"},{"name":"Department of Neurology, National Hospital Organization, Matsumoto Medical Center, Matsumoto 399-8701, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6672-6742","authenticated-orcid":false,"given":"Toshifumi","family":"Yokota","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G2H7, Canada"},{"name":"The Friends of Garrett Cumming Research and Muscular Dystrophy Canada HM Toupin Neurological Science Endowed Research Chair, Edmonton, AB, T6G2H7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,12,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/0092-8674(87)90504-6","article-title":"Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals","volume":"50","author":"Koenig","year":"1987","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/0092-8674(87)90579-4","article-title":"Dystrophin: The protein product of the Duchenne muscular dystrophy locus","volume":"51","author":"Hoffman","year":"1987","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.nmd.2014.03.008","article-title":"A systematic review and meta-analysis on the epidemiology of Duchenne and Becker muscular dystrophy","volume":"24","author":"Mah","year":"2014","journal-title":"Neuromuscul. 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