{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T02:55:02Z","timestamp":1791600902928,"version":"4.3.4"},"reference-count":206,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000223","name":"Muscular Dystrophy Canada","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000223","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Friends of Garrett Cumming Research Fund"},{"name":"HM Toupin Neurological Science Research Fund"},{"DOI":"10.13039\/501100000024","name":"Canadian Institute of Health Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000145","name":"Alberta Innovates: Health Solutions","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000145","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Jesse\u2019s Journey"},{"name":"Women and Children\u2019s Health Research Institute"},{"name":"Heart and Stroke Foundation Canada"},{"DOI":"10.13039\/100000005","name":"US Department of Defense","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100019691","name":"University of Alberta Faculty of Medicine and Dentistry","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100019691","id-type":"DOI","asserted-by":"crossref"}]},{"name":"CIHR Strategic Master\u2019s Award"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Rare neuromuscular disorders impose a significant burden on patients, caregivers, and the health care system, yet, effective disease-modifying therapies remain limited. Antisense oligonucleotides (ASOs) have emerged as a promising therapeutic strategy, enabling targeted modulation of gene expression through mechanisms such as exon skipping, exon inclusion, and transcript degradation. However, the clinical efficacy of currently approved ASO therapies is often suboptimal. This limitation reflects not only poor target tissue uptake and delivery barriers, but also suboptimal design of ASO sequences and chemical modification patterns, which can compromise potency, safety, and translational robustness. Recent advances in machine learning have led to the development of ASO optimization platforms such as eSkipFinder and ASOptimizer, which aim to predict effective ASO sequences and chemistries for specific RNA targets. While these tools show considerable promise, their broader applicability remains limited due to a lack of comprehensive validation and the absence of integrated safety considerations. Further refinement and validation are necessary to improve their translational utility. Nevertheless, such platforms represent a critical advancement toward accelerating ASO development. By improving design precision, reducing reliance on extensive preclinical screening, and enabling researchers with limited ASO experience to generate optimized candidates, machine learning is poised to accelerate the development and clinical translation of ASO therapies for rare neuromuscular disorders.<\/jats:p>","DOI":"10.3390\/genes16121468","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T14:52:24Z","timestamp":1765205544000},"page":"1468","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Artificial Intelligence-Driven Design of Antisense Oligonucleotides for Precision Medicine in Neuromuscular Disorders"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3166-8973","authenticated-orcid":false,"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":"Sunny","family":"Wu","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"}]},{"given":"Terryanne","family":"Standell","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":[[2025,12,8]]},"reference":[{"key":"ref_1","first-page":"633","article-title":"The Direct Cost of Managing a Rare Disease: Assessing Medical and Pharmacy Costs Associated with Duchenne Muscular Dystrophy in the United States","volume":"23","author":"Thayer","year":"2017","journal-title":"J. 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