{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T02:48:21Z","timestamp":1790131701755,"version":"4.0.1"},"reference-count":26,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Nucleic Acid Therapeutics"],"published-print":{"date-parts":[[2025,4,1]]},"abstract":"<jats:p>\n                    Exon skipping with antisense oligonucleotides (ASOs) can correct disease-causing mutations of Duchenne muscular dystrophy (DMD) through RNA-targeted splice correction. This correction restores the reading frame and supports expression of near full-length dystrophin. First-generation exon 51-skipping ASOs targeted the same binding site, with limited clinical efficacy. We characterized a novel binding site within exon 51 that induced highly efficient exon skipping. A precursor ASO (AON-C12) and clinical ASO (BMN 351) were designed using 2\u2032-\n                    <jats:italic toggle=\"yes\">O<\/jats:italic>\n                    -methyl-modified phosphorothioate (2\u2032OMePS) RNA and locked nucleic acids. hDMDdel52\/\n                    <jats:italic toggle=\"yes\">mdx<\/jats:italic>\n                    mice were given AON-C12 or BMN 351 for 13 weeks and evaluated for molecular and phenotypic correction of dystrophin deficiency. BMN 351 treatment induced durable, dose-dependent levels of exon skipping and dystrophin production in all muscles evaluated. In the heart, 8 weeks after the last BMN 351 dose at 18 mg\/kg, exon-skipped transcripts remained at 44.3% of total, and dystrophin levels were 21.8% of wild type. BMN 351 reached higher tissue concentrations and percent exon skipping in the heart than a clinically relevant peptide-conjugated phosphorodiamidate morpholino oligomer comparator. BMN 351 also improved gait scores and clinical and anatomical muscle pathology parameters compared with vehicle-treated hDMDdel52\/\n                    <jats:italic toggle=\"yes\">mdx<\/jats:italic>\n                    mice. The pharmacologic activity and safety of BMN 351 warrant further nonclinical and clinical development.\n                  <\/jats:p>","DOI":"10.1089\/nat.2024.0049","type":"journal-article","created":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T03:21:07Z","timestamp":1738898467000},"page":"68-80","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["Targeting a Novel Site in Exon 51 with Antisense Oligonucleotides Induces Enhanced Exon Skipping in a Mouse Model of Duchenne Muscular Dystrophy"],"prefix":"10.1177","volume":"35","author":[{"given":"Todd","family":"Oppeneer","sequence":"first","affiliation":[{"name":"BioMarin Pharmaceutical Inc., San Rafael, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulan","family":"Qi","sequence":"additional","affiliation":[{"name":"BioMarin Pharmaceutical Inc., San Rafael, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Henshaw","sequence":"additional","affiliation":[{"name":"BioMarin Pharmaceutical Inc., San Rafael, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Larimore","sequence":"additional","affiliation":[{"name":"BioMarin Pharmaceutical Inc., San Rafael, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Melton","sequence":"additional","affiliation":[{"name":"BioMarin Pharmaceutical Inc., San Rafael, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jukka","family":"Puoliv\u00e4li","sequence":"additional","affiliation":[{"name":"Charles River Discovery Research Services, Kuopio, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlyn","family":"Carter","sequence":"additional","affiliation":[{"name":"Charles River Laboratories, Inc., Mattawan, MI, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierluigi","family":"Fant","sequence":"additional","affiliation":[{"name":"Charles River Laboratories France Safety Assessment SAS, Saint-Germain-Nuelles, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Brennan","sequence":"additional","affiliation":[{"name":"BioMarin Pharmaceutical Inc., San Rafael, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura A.","family":"Wetzel","sequence":"additional","affiliation":[{"name":"BioMarin Pharmaceutical Inc., San Rafael, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika A.","family":"Sigg","sequence":"additional","affiliation":[{"name":"BioMarin Pharmaceutical Inc., San Rafael, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brett E.","family":"Crawford","sequence":"additional","affiliation":[{"name":"BioMarin Pharmaceutical Inc., San Rafael, CA, 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