{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T13:49:36Z","timestamp":1765547376264,"version":"build-2065373602"},"reference-count":117,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T00:00:00Z","timestamp":1737676800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Muscular Dystrophy Canada"},{"name":"the Friends of Garrett Cumming Research Fund"},{"name":"the HM Toupin Neurological Science Research Fund"},{"name":"the Canadian Institute of Health Research (CIHR)"},{"name":"Alberta Innovates: Health Solutions (AIHS)"},{"name":"Jesse\u2019s Journey"},{"name":"the Women and Children\u2019s Health Research Institute (WCHRI)"},{"name":"the Heart and Stroke Foundation Canada"},{"name":"the US Department of Defense"},{"name":"scholarships from the University of Alberta Faculty of Medicine"},{"name":"Dentistry and the CIHR Strategic Master\u2019s Award"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Exon skipping, mediated through antisense oligonucleotides (ASOs), is a promising approach to exclude pathogenic variants from the DYSF gene and treat dysferlinopathies. Understanding the applicability of various exon skipping strategies in the total patient population, an analysis not previously performed, can help guide researchers in prioritizing therapies with the broadest potential impact. Using data from the UMD-DYSF database, we evaluated all reported pathogenic variants in dysferlinopathy patients for the applicability of single- or double-exon skipping approaches to exclude the pathogenic variants while maintaining the open reading frame. A total of 61 theoretically applicable exon skipping strategies were identified, with the potential to address 90.0% of the pathogenic variants reported\u201444.6% through single-exon skipping and 45.3% through double-exon skipping. The most broadly applicable targets include exons 28 and 29 (9.0%), exons 27 and 28 (6.7%), and exons 50 and 51 (5.4%). While numerous theoretically applicable strategies were identified, it remains unclear if the truncated proteins produced through each exon skipping strategy will have improved functionality to alleviate patient symptoms. Further preclinical studies and clinical trials will be essential to determine the effectiveness of these therapies, potentially expanding access to disease-modifying treatments for dysferlinopathy patients.<\/jats:p>","DOI":"10.3390\/cells14030177","type":"journal-article","created":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T03:26:31Z","timestamp":1737689191000},"page":"177","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Analysis of Exon Skipping Applicability for Dysferlinopathies"],"prefix":"10.3390","volume":"14","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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian Hernandez","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2H7, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Krahn","sequence":"additional","affiliation":[{"name":"INSERM, Marseille Medical Genetics, U1251, Aix-Marseille University, APHM, 13385 Marseille, France"},{"name":"Medical Genetics Department, Timone Hospital, APHM, 13005 Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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 T6G 2H7, Canada"},{"name":"The Friends of Garrett Cumming Research & Muscular Dystrophy Canada HM Toupin Neurological Sciences Research, Edmonton, AB T6G 2H7, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Anwar, S., He, M., Lim, K.R.Q., Maruyama, R., and Yokota, T. 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