{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:10:09Z","timestamp":1787008209228,"version":"build-2736575974"},"reference-count":39,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2022,1,27]],"date-time":"2022-01-27T00:00:00Z","timestamp":1643241600000},"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":[[2022,6,1]]},"abstract":"<jats:p>\n                    Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder characterized by episodic heterotopic ossification. The median life span of people with this disorder is \u223c40 years, and currently, there is no effective treatment available. More than 95% of cases are caused by a recurrent mutation (c.617G&gt;A; R206H) of Activin A receptor, type I (ACVR1)\/Activin receptor-like kinase-2 (ALK2), a bone morphogenetic protein type I receptor. The mutation renders ACVR1 responsive to activin A, which does not activate wild-type ACVR1. Ectopic activation of ACVR1\n                    <jats:sup>R206H<\/jats:sup>\n                    by activin A induces heterotopic ossification. Since ACVR1\n                    <jats:sup>R206H<\/jats:sup>\n                    is a hyperactive receptor, a promising therapeutic strategy is to decrease the activity of mutated ACVR1. To accomplish this goal, we developed locked nucleic acid (LNA) gapmers. These are short DNA oligonucleotides with LNA modification at both ends. They induce targeted mRNA degradation and specific knockdown of gene expression. We demonstrated that some of these gapmers efficiently knocked down ACVR1\n                    <jats:sup>R206H<\/jats:sup>\n                    expression at RNA levels, while ACVR1\n                    <jats:sup>WT<\/jats:sup>\n                    was mostly unaffected in human FOP fibroblasts. Also, the gapmers suppressed osteogenic differentiation induced by ACVR1\n                    <jats:sup>R206H<\/jats:sup>\n                    and activin A. These gapmers may be promising drug candidates for FOP. This novel strategy will also pave the way for antisense-mediated therapy of other autosomal dominant disorders.\n                  <\/jats:p>","DOI":"10.1089\/nat.2021.0009","type":"journal-article","created":{"date-parts":[[2022,1,27]],"date-time":"2022-01-27T17:33:56Z","timestamp":1643304836000},"page":"185-193","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":12,"title":["Allele-Selective LNA Gapmers for the Treatment of Fibrodysplasia Ossificans Progressiva Knock Down the Pathogenic ACVR1\n                    <sup>R206H<\/sup>\n                    Transcript and Inhibit Osteogenic Differentiation"],"prefix":"10.1177","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5656-6930","authenticated-orcid":false,"given":"Rika","family":"Maruyama","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quynh","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohini Roy","family":"Roshmi","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksander","family":"Touznik","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshifumi","family":"Yokota","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada."},{"name":"The Friends of Garrett Cumming Research &amp; Muscular Dystrophy Canada HM Toupin Neurological Science Research Chair, Edmonton, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2022,1,27]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-6-80"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1783"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1159\/000365770"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aac4358"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1510540112"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaf1090"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-02872-2"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2820"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI93521"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2018.10.007"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1638"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.126.11.2551"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1999.9378"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mod.2003.12.003"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.40814"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2011.152"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2011.193"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0107434"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2014.153"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aar3959"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000323"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.10.5633"},{"key":"e_1_3_5_24_2","first-page":"57530","article-title":"Evaluation of exon inclusion induced by splice switching antisense oligonucleotides in SMA patient fibroblasts","volume":"135","author":"Maruyama R","year":"2018","unstructured":"Maruyama R, , Touznik A, and Yokota. 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