{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T19:45:48Z","timestamp":1777923948180,"version":"3.51.4"},"reference-count":63,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2019,3,29]],"date-time":"2019-03-29T00:00:00Z","timestamp":1553817600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,3,29]],"date-time":"2019-03-29T00:00:00Z","timestamp":1553817600000},"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":[[2019,4,1]]},"abstract":"<jats:p>\n                    Duchenne muscular dystrophy is a severe, progressive muscle-wasting disease that is caused by mutations that abolish the production of functional dystrophin protein. The exon skipping approach aims to restore the disrupted dystrophin reading frame, to allow the production of partially functional dystrophins, such as found in the less severe Becker muscular dystrophy. Exon skipping is achieved by antisense oligonucleotides (AONs). Several chemical modifications have been tested in nonclinical and clinical trials. The morpholino phosphorodiamidate oligomer eteplirsen has been approved by the Food and Drug Administration, whereas clinical development with the 2\u2032-\n                    <jats:italic toggle=\"yes\">O<\/jats:italic>\n                    -methyl phosphorothioate (2OMePS) AON drisapersen was recently stopped. In this study, we aimed to study various aspects of 2OMePS AONs in nonclinical animal studies. We show that while efficiency of exon skipping restoration is comparable in young and older C57BL\/10ScSn-\n                    <jats:italic toggle=\"yes\">\n                      Dmd\n                      <jats:sup>mdx<\/jats:sup>\n                    <\/jats:italic>\n                    \/J (\n                    <jats:italic toggle=\"yes\">mdx<\/jats:italic>\n                    \/BL10) mice, functional improvement was only observed for younger treated mice. Muscle quality did not affect exon skipping efficiency as exon skip and dystrophin levels were similar between\n                    <jats:italic toggle=\"yes\">mdx<\/jats:italic>\n                    \/BL10 and more severely affected, age-matched D2-\n                    <jats:italic toggle=\"yes\">mdx<\/jats:italic>\n                    mice. We further report that treadmill running increases AON uptake and dystrophin levels in\n                    <jats:italic toggle=\"yes\">mdx<\/jats:italic>\n                    \/BL10 mice. Finally, we show that even low levels of exon skipping and dystrophin restoration are sufficient to significantly increase the survival of\n                    <jats:italic toggle=\"yes\">mdx-utrn<\/jats:italic>\n                    \u2212\/\u2212 mice from 70 to 97 days.\n                  <\/jats:p>","DOI":"10.1089\/nat.2018.0759","type":"journal-article","created":{"date-parts":[[2019,1,23]],"date-time":"2019-01-23T10:30:48Z","timestamp":1548239448000},"page":"92-103","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":9,"title":["Nonclinical Exon Skipping Studies with 2\u2032-\n                    <i>O<\/i>\n                    -Methyl Phosphorothioate Antisense Oligonucleotides in\n                    <i>mdx<\/i>\n                    and\n                    <i>mdx-utrn\u2212\/\u2212<\/i>\n                    Mice Inspired by Clinical Trial Results"],"prefix":"10.1177","volume":"29","author":[{"given":"Maaike","family":"van Putten","sequence":"first","affiliation":[{"name":"Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christa","family":"Tanganyika-De Winter","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sieto","family":"Bosgra","sequence":"additional","affiliation":[{"name":"Biomarin Nederland BV, Leiden, the Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annemieke","family":"Aartsma-Rus","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Leiden University Medical Center, Leiden, the 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