{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T19:39:38Z","timestamp":1786390778748,"version":"build-2736575974"},"reference-count":44,"publisher":"National Academy of Sciences","issue":"33","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01 GM042699"],"award-info":[{"award-number":["R01 GM042699"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002350","name":"St. Giles Foundation","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100002350","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ASOcura Pharmaceuticals","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"Nanjing Antisense Biopharm","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,8,18]]},"abstract":"<jats:p>\n                    Antisense-mediated exon skipping has been used to treat Duchenne muscular dystrophy (DMD) by restoring the\n                    <jats:italic toggle=\"yes\">DMD<\/jats:italic>\n                    reading frame to express partially functional dystrophin. However, difficulty in designing effective antisense oligonucleotides (ASOs) has hindered the development of clinically effective therapies. Here we describe a robust bipartite ASO design, termed 5\u2032 splice site decoy (5D)-ASO, in which a short tail sequence is employed to enhance the splicing repression exerted by an antisense moiety. The tail carried by the antisense moiety to an exon of interest in a target pre-mRNA interferes with the recognition of the exon\u2019s 5\u2032 splice site by U1 snRNA and markedly enhances exon skipping, compared to tail-less ASOs. 5D-ASO has broad applicability, based on multiple genes tested. Particularly, an 8-nt tail, when appended to sequences targeting\n                    <jats:italic toggle=\"yes\">DMD<\/jats:italic>\n                    exon 51, elicited a pronounced increase in exon skipping in mouse models, restored dystrophin expression in muscle tissues and improved the phenotype, without obvious signs of toxicity. The lead ASO further demonstrated a marked exon-skipping effect and an overall safe profile in monkeys. Our data establish a valuable platform technology for RNA-targeted therapeutics.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2606494123","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T19:09:16Z","timestamp":1786388956000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["An antisense method for efficient exon skipping and its application to Duchenne muscular dystrophy"],"prefix":"10.1073","volume":"123","author":[{"given":"Pengchao","family":"Feng","sequence":"first","affiliation":[{"name":"Nanjing Antisense Biopharm","place":["Nanjing, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Gao","sequence":"additional","affiliation":[{"name":"Nanjing Antisense Biopharm","place":["Nanjing, Jiangsu, China"]},{"id":[{"id":"https:\/\/ror.org\/036trcv74","id-type":"ROR","asserted-by":"publisher"}],"name":"Jiangsu Key Laboratory for 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