{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:58:51Z","timestamp":1791939531013,"version":"4.3.4"},"reference-count":120,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T00:00:00Z","timestamp":1732060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Muscular Dystrophy Canada"},{"name":"Friends of Garrett Cumming Research Fund"},{"name":"HM Toupin Neurological Science Research Fund"},{"name":"Canadian Institute of Health Research (CIHR)"},{"name":"Alberta Innovates: Health Solutions (AIHS)"},{"name":"Jesse\u2019s Journey"},{"name":"Women and Children\u2019s Health Research Institute (WCHRI)"},{"name":"Heart and Stroke Foundation Canada"},{"name":"US Department of Defense"},{"name":"University of Alberta Faculty of Medicine and Dentistry"},{"name":"CIHR Strategic Master\u2019s Award"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Antisense oligonucleotide (ASO)-mediated exon-skipping is an effective approach to restore the disrupted reading frame of the dystrophin gene for the treatment of Duchenne muscular dystrophy (DMD). Currently, four FDA-approved ASOs can target three different exons, but these therapies are mutation-specific and only benefit a subset of patients. Understanding the broad applicability of exon-skipping approaches is essential for prioritizing the development of additional therapies with the greatest potential impact on the DMD population. This review offers an updated analysis of all theoretical exon-skipping strategies and their applicability across the patient population, with a specific focus on DMD-associated mutations documented in the UMD-DMD database. Unlike previous studies, this approach leverages the inclusion of phenotypic data for each mutation, providing a more comprehensive and clinically relevant perspective. Methods: The theoretical applicability of all single and double exon-skipping strategies, along with multi exon-skipping strategies targeting exons 3\u20139 and 45\u201355, was evaluated for all DMD mutations reported in the UMD-DMD database. Results: Single and double exon-skipping approaches were applicable for 92.8% of large deletions, 93.7% of small lesions, 72.4% of duplications, and 90.3% of all mutations analyzed. Exon 51 was the most relevant target and was applicable for 10.6% of all mutations and 17.2% of large deletions. Additionally, two multi-exon-skipping approaches, targeting exons 45\u201355 and 3\u20139, were relevant for 70.6% of large deletions and 19.2% of small lesions. Conclusions: Current FDA-approved ASOs were applicable to 27% of the UMD-DMD population analyzed, leaving a significant portion of patients without access to exon-skipping therapies. The clinical translation of alternative approaches is critical to expanding the accessibility of these therapies for the DMD population.<\/jats:p>","DOI":"10.3390\/genes15111489","type":"journal-article","created":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T07:02:58Z","timestamp":1732086178000},"page":"1489","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["An Updated Analysis of Exon-Skipping Applicability for Duchenne Muscular Dystrophy Using the UMD-DMD Database"],"prefix":"10.3390","volume":"15","author":[{"given":"Jamie","family":"Leckie","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2H7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah","family":"Zia","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2H7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7316-3546","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 T6G 2H7, Canada"},{"name":"The Friends of Garrett Cumming Research & Muscular Dystrophy Canada HM Toupin Neurological Sciences Research, Edmonton, AB T6G 2H7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,20]]},"reference":[{"key":"ref_1","first-page":"94","article-title":"Markers of degeneration and regeneration in Duchenne muscular dystrophy","volume":"28","author":"Korraa","year":"2009","journal-title":"Acta Myol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Anwar, S., He, M., Lim, K.R.Q., Maruyama, R., and Yokota, T. 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