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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2020,7,14]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    Facioscapulohumeral dystrophy (FSHD) is an inherited disabling muscular disorder caused by misexpression of\n                    <jats:italic>DUX4<\/jats:italic>\n                    in skeletal muscles. FSHD has variable onset; its infantile form has a more severe disease course. There is no cure for FSHD. Here, we show the potential of antisense oligonucleotides called locked nucleic acid (LNA) gapmers for treating FSHD. We designed LNA gapmers to knock down\n                    <jats:italic>DUX4<\/jats:italic>\n                    messenger RNA and found that its expression was effectively reduced in patient-derived cells and an FSHD mouse model. Functional benefits and minimal off-targeting were observed in vitro. Our study facilitates progress toward finding new candidates for treating FSHD. The screening protocol used here for antisense oligonucleotides targeting\n                    <jats:italic>DUX4<\/jats:italic>\n                    can also be adapted by other efforts developing similar treatments for FSHD.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1909649117","type":"journal-article","created":{"date-parts":[[2020,6,29]],"date-time":"2020-06-29T20:37:54Z","timestamp":1593463074000},"page":"16509-16515","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":53,"title":["Inhibition of\n                    <i>DUX4<\/i>\n                    expression with antisense LNA gapmers as a therapy for facioscapulohumeral muscular dystrophy"],"prefix":"10.1073","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5484-4183","authenticated-orcid":false,"given":"Kenji Rowel Q.","family":"Lim","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G2H7, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5656-6930","authenticated-orcid":false,"given":"Rika","family":"Maruyama","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G2H7, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1573-4819","authenticated-orcid":false,"given":"Yusuke","family":"Echigoya","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G2H7, Canada;"},{"name":"Laboratory of Biomedical Science, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, Fujisawa, Kanagawa, 252-0880, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1330-9026","authenticated-orcid":false,"given":"Quynh","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G2H7, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for Genetic Medicine Research, Children\u2019s National Health System, Washington, DC 20010;"},{"name":"Department of Integrative Systems Biology, George Washington University, Washington, DC 20052;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hunain","family":"Khawaja","sequence":"additional","affiliation":[{"name":"Center for Genetic Medicine Research, Children\u2019s National Health System, Washington, DC 20010;"},{"name":"Department of Integrative Systems Biology, George Washington University, Washington, DC 20052;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sreetama","family":"Sen Chandra","sequence":"additional","affiliation":[{"name":"Center for Genetic Medicine Research, Children\u2019s National Health System, Washington, DC 20010;"},{"name":"Department of Integrative Systems Biology, George Washington University, Washington, DC 20052;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takako","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Nevada Reno School of Medicine, Reno, NV 89557-0318;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Nevada Reno School of Medicine, Reno, NV 89557-0318;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Wen","family":"Chen","sequence":"additional","affiliation":[{"name":"Center for Genetic Medicine Research, Children\u2019s National Health System, Washington, DC 20010;"},{"name":"Department of Genomics and Precision Medicine, School of Medicine and Health Science, George Washington University, Washington, DC 20052;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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 T6G2H7, Canada;"},{"name":"The Friends of Garrett Cumming Research &amp; 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