{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T14:53:44Z","timestamp":1793199224842,"version":"4.5.0"},"reference-count":78,"publisher":"National Academy of Sciences","issue":"22","license":[{"start":{"date-parts":[[2021,10,30]],"date-time":"2021-10-30T00:00:00Z","timestamp":1635552000000},"content-version":"vor","delay-in-days":183,"URL":"https:\/\/www.pnas.org\/site\/aboutpnas\/licenses.xhtml"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["HL130253"],"award-info":[{"award-number":["HL130253"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["AR067294"],"award-info":[{"award-number":["AR067294"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["U54HD087351"],"award-info":[{"award-number":["U54HD087351"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000928","name":"Welch Foundation","doi-asserted-by":"publisher","award":["1-0025"],"award-info":[{"award-number":["1-0025"]}],"id":[{"id":"10.13039\/100000928","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:p>Recent advances in gene editing technologies are enabling the potential correction of devastating monogenic disorders through elimination of underlying genetic mutations. Duchenne muscular dystrophy (DMD) is an especially severe genetic disorder caused by mutations in the gene encoding dystrophin, a membrane-associated protein required for maintenance of muscle structure and function. Patients with DMD succumb to loss of mobility early in life, culminating in premature death from cardiac and respiratory failure. The disease has thus far defied all curative strategies. CRISPR gene editing has provided new opportunities to ameliorate the disease by eliminating DMD mutations and thereby restore dystrophin expression throughout skeletal and cardiac muscle. Proof-of-concept studies in rodents, large mammals, and human cells have validated the potential of this approach, but numerous challenges remain to be addressed, including optimization of gene editing, delivery of gene editing components throughout the musculature, and mitigation of possible immune responses. This paper provides an overview of recent work from our laboratory and others toward the genetic correction of DMD and considers the opportunities and challenges in the path to clinical translation. Lessons learned from these studies will undoubtedly enable further applications of gene editing to numerous other diseases of muscle and other tissues.<\/jats:p>","DOI":"10.1073\/pnas.2004840117","type":"journal-article","created":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T12:48:44Z","timestamp":1622551724000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":77,"title":["Toward the correction of muscular dystrophy by gene editing"],"prefix":"10.1073","volume":"118","author":[{"given":"Eric N.","family":"Olson","sequence":"first","affiliation":[{"name":"Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390;"},{"name":"Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390;"},{"name":"Paul D. Wellstone Muscular Dystrophy Cooperative Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2021,4,30]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2019.10.010"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-1978-5"},{"key":"e_1_3_4_3_2","volume-title":"GeneReviews","author":"Darras B. T.","year":"1993","unstructured":"B. T. Darras, D. K. Urion, P. S. Ghosh, \u201cDystrophinopathies\u201d in GeneReviews, M. P. Adam ., Eds. (University of Washington, Seattle, WA, 1993)."},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1006\/mgme.2001.3220"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(03)00585-4"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22758"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0493-283"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/338259a0"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0888-7543(88)90113-9"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1080\/00207454.2018.1430694"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1080\/17460441.2020.1718100"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2012.234"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S97635"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/343180a0"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm158"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2018.07.011"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1080\/14712598.2020.1725469"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1225829"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1231143"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1232033"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00046.2017"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-081117-010451"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI136873"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00012.2019"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.3390\/jpm8040038"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2007.07.005"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2016.041"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv155"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/mtna.2015.58"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1254445"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.1602814"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2014.10.013"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7244"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad5725"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aan8081"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aap9004"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.3233\/JND-170218"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep37051"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.95918"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aav4324"},{"key":"e_1_3_4_41_2","article-title":"Correction of three prominent mutations in mouse and human models of Duchenne muscular dystrophy by single-cut genome editing","author":"Min Y. L.","unstructured":"Y. L. Min ., Correction of three prominent mutations in mouse and human models of Duchenne muscular dystrophy by single-cut genome editing. Mol. Ther., in press.","journal-title":"Mol. Ther."},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.124297"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aay6812"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad5143"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad5177"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2015.192"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14454"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2019.06.012"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2019.05.001"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2018.08.010"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0344-3"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2008.197"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1002\/biot.201400046"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.3233\/JND-170267"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aau1549"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0738-2"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12335-x"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/mtm.2014.38"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2014.12.001"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4192"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0500-9"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature16526"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature24268"},{"key":"e_1_3_4_64_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12449-2"},{"key":"e_1_3_4_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.03.023"},{"key":"e_1_3_4_66_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-019-0205-4"},{"key":"e_1_3_4_67_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-017-0137-2"},{"key":"e_1_3_4_68_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17029-3"},{"key":"e_1_3_4_69_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2009.182"},{"key":"e_1_3_4_70_2","doi-asserted-by":"publisher","DOI":"10.1089\/hgtb.2012.243"},{"key":"e_1_3_4_71_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0326-x"},{"key":"e_1_3_4_72_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05843-9"},{"key":"e_1_3_4_73_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0204-6"},{"key":"e_1_3_4_74_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2018.06.006"},{"key":"e_1_3_4_75_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-019-0431-2"},{"key":"e_1_3_4_76_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0911-7"},{"key":"e_1_3_4_77_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09693-x"},{"key":"e_1_3_4_78_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4148"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.2004840117","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2004840117","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T06:39:15Z","timestamp":1649831955000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.2004840117"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,30]]},"references-count":78,"journal-issue":{"issue":"22","published-print":{"date-parts":[[2021,6]]}},"alternative-id":["10.1073\/pnas.2004840117"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2004840117","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,30]]},"assertion":[{"value":"2021-04-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2004840117"}}