{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T19:15:52Z","timestamp":1790795752734,"version":"4.1.0"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2017,7,17]],"date-time":"2017-07-17T00:00:00Z","timestamp":1500249600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Med"],"published-print":{"date-parts":[[2017,8]]},"DOI":"10.1038\/nm.4367","type":"journal-article","created":{"date-parts":[[2017,7,17]],"date-time":"2017-07-17T11:08:29Z","timestamp":1500289709000},"page":"984-989","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":75,"title":["Correction of a splicing defect in a mouse model of congenital muscular dystrophy type 1A using a homology-directed-repair-independent mechanism"],"prefix":"10.1038","volume":"23","author":[{"given":"Dwi U","family":"Kemaladewi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Maino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elzbieta","family":"Hyatt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huayun","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maylynn","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kara M","family":"Place","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prabhpreet","family":"Bassi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahra","family":"Baghestani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit G","family":"Deshwar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Merico","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui Y","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan J","family":"Frey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4015-3066","authenticated-orcid":false,"given":"Michael D","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evgueni A","family":"Ivakine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald D","family":"Cohn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,7,17]]},"reference":[{"key":"BFnm4367_CR1","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1038\/nrg.2015.3","volume":"17","author":"MM Scotti","year":"2016","unstructured":"Scotti, M.M. & Swanson, M.S. RNA mis-splicing in disease. Nat. Rev. Genet. 17, 19\u201332 (2016).","journal-title":"Nat. Rev. Genet."},{"key":"BFnm4367_CR2","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1002\/humu.22758","volume":"36","author":"CL Bladen","year":"2015","unstructured":"Bladen, C.L. et al. The TREAT-NMD DMD Global Database: analysis of more than 7,000 Duchenne muscular dystrophy mutations. Hum. Mutat. 36, 395\u2013402 (2015).","journal-title":"Hum. Mutat."},{"key":"BFnm4367_CR3","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1038\/nbt.3469","volume":"34","author":"Y Yang","year":"2016","unstructured":"Yang, Y. et al. A dual AAV system enables the Cas9-mediated correction of a metabolic liver disease in newborn mice. Nat. Biotechnol. 34, 334\u2013338 (2016).","journal-title":"Nat. Biotechnol."},{"key":"BFnm4367_CR4","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1038\/nbt.2884","volume":"32","author":"H Yin","year":"2014","unstructured":"Yin, H. et al. Genome editing with Cas9 in adult mice corrects a disease mutation and phenotype. Nat. Biotechnol. 32, 551\u2013553 (2014).","journal-title":"Nat. Biotechnol."},{"key":"BFnm4367_CR5","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1038\/nbt.3471","volume":"34","author":"H Yin","year":"2016","unstructured":"Yin, H. et al. Therapeutic genome editing by combined viral and non-viral delivery of CRISPR system components in vivo. Nat. Biotechnol. 34, 328\u2013333 (2016).","journal-title":"Nat. Biotechnol."},{"issue":"3 Pt A","key":"BFnm4367_CR6","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1016\/j.scr.2014.08.005","volume":"13","author":"L Vahidi Ferdousi","year":"2014","unstructured":"Vahidi Ferdousi, L. et al. More efficient repair of DNA double-strand breaks in skeletal muscle stem cells compared to their committed progeny. Stem Cell Res. 13 3 Pt A, 492\u2013507 (2014).","journal-title":"Stem Cell Res."},{"key":"BFnm4367_CR7","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/bs.ctm.2015.05.002","volume":"76","author":"M Durbeej","year":"2015","unstructured":"Durbeej, M. Laminin-\u03b12 chain-deficient congenital muscular dystrophy: pathophysiology and development of treatment. Curr. Top. Membr. 76, 31\u201360 (2015).","journal-title":"Curr. Top. Membr."},{"key":"BFnm4367_CR8","doi-asserted-by":"publisher","first-page":"1055","DOI":"10.1093\/hmg\/4.6.1055","volume":"4","author":"Y Sunada","year":"1995","unstructured":"Sunada, Y., Bernier, S.M., Utani, A., Yamada, Y. & Campbell, K.P. Identification of a novel mutant transcript of laminin alpha 2 chain gene responsible for muscular dystrophy and dysmyelination in dy2J mice. Hum. Mol. Genet. 4, 1055\u20131061 (1995).","journal-title":"Hum. Mol. Genet."},{"key":"BFnm4367_CR9","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.nmd.2010.02.001","volume":"20","author":"F Geranmayeh","year":"2010","unstructured":"Geranmayeh, F. et al. Genotype-phenotype correlation in a large population of muscular dystrophy patients with LAMA2 mutations. Neuromuscul. Disord. 20, 241\u2013250 (2010).","journal-title":"Neuromuscul. Disord."},{"key":"BFnm4367_CR10","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1146\/annurev-genom-090314-025003","volume":"16","author":"S Guiraud","year":"2015","unstructured":"Guiraud, S. et al. The pathogenesis and therapy of muscular dystrophies. Annu. Rev. Genomics Hum. Genet. 16, 281\u2013308 (2015).","journal-title":"Annu. Rev. Genomics Hum. Genet."},{"key":"BFnm4367_CR11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00439-013-1358-4","volume":"133","author":"PD Stenson","year":"2014","unstructured":"Stenson, P.D. et al. The Human Gene Mutation Database: building a comprehensive mutation repository for clinical and molecular genetics, diagnostic testing and personalized genomic medicine. Hum. Genet. 133, 1\u20139 (2014).","journal-title":"Hum. Genet."},{"key":"BFnm4367_CR12","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1038\/ng1194-297","volume":"8","author":"H Xu","year":"1994","unstructured":"Xu, H., Wu, X.R., Wewer, U.M. & Engvall, E. Murine muscular dystrophy caused by a mutation in the laminin alpha 2 (Lama2) gene. Nat. Genet. 8, 297\u2013302 (1994).","journal-title":"Nat. Genet."},{"key":"BFnm4367_CR13","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1126\/science.1225829","volume":"337","author":"M Jinek","year":"2012","unstructured":"Jinek, M. et al. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337, 816\u2013821 (2012).","journal-title":"Science"},{"key":"BFnm4367_CR14","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1038\/nature14299","volume":"520","author":"FA Ran","year":"2015","unstructured":"Ran, F.A. et al. In vivo genome editing using Staphylococcus aureus Cas9. Nature 520, 186\u2013191 (2015).","journal-title":"Nature"},{"key":"BFnm4367_CR15","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1101\/gad.209759.112","volume":"27","author":"X Roca","year":"2013","unstructured":"Roca, X., Krainer, A.R. & Eperon, I.C. Pick one, but be quick: 5\u2032 splice sites and the problems of too many choices. Genes Dev. 27, 129\u2013144 (2013).","journal-title":"Genes Dev."},{"key":"BFnm4367_CR16","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1172\/JCI3705","volume":"102","author":"W Kuang","year":"1998","unstructured":"Kuang, W. et al. Merosin-deficient congenital muscular dystrophy. Partial genetic correction in two mouse models. J. Clin. Invest. 102, 844\u2013852 (1998).","journal-title":"J. Clin. Invest."},{"key":"BFnm4367_CR17","doi-asserted-by":"publisher","first-page":"36","DOI":"10.3389\/fnmol.2015.00036","volume":"8","author":"Y Tanguy","year":"2015","unstructured":"Tanguy, Y. et al. Systemic AAVrh10 provides higher transgene expression than AAV9 in the brain and the spinal cord of neonatal mice. Front. Mol. Neurosci. 8, 36 (2015).","journal-title":"Front. Mol. Neurosci."},{"key":"BFnm4367_CR18","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1038\/mt.2008.76","volume":"16","author":"C Zincarelli","year":"2008","unstructured":"Zincarelli, C., Soltys, S., Rengo, G. & Rabinowitz, J.E. Analysis of AAV serotypes 1-9 mediated gene expression and tropism in mice after systemic injection. Mol. Ther. 16, 1073\u20131080 (2008).","journal-title":"Mol. Ther."},{"key":"BFnm4367_CR19","first-page":"e52037","volume":"93","author":"SE Gombash Lampe","year":"2014","unstructured":"Gombash Lampe, S.E., Kaspar, B.K. & Foust, K.D. Intravenous injections in neonatal mice. J. Vis. Exp. 93, e52037 (2014).","journal-title":"J. Vis. Exp."},{"key":"BFnm4367_CR20","doi-asserted-by":"publisher","first-page":"e65468","DOI":"10.1371\/journal.pone.0065468","volume":"8","author":"Q Yu","year":"2013","unstructured":"Yu, Q. et al. Omigapil treatment decreases fibrosis and improves respiratory rate in dy(2J) mouse model of congenital muscular dystrophy. PLoS One 8, e65468 (2013).","journal-title":"PLoS One"},{"key":"BFnm4367_CR21","first-page":"51785","volume":"91","author":"KS Tatem","year":"2014","unstructured":"Tatem, K.S. et al. Behavioral and locomotor measurements using an open field activity monitoring system for skeletal muscle diseases. J. Vis. Exp. 91, 51785 (2014).","journal-title":"J. Vis. Exp."},{"key":"BFnm4367_CR22","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1007\/978-1-4939-3810-0_20","volume":"1460","author":"SR Iyer","year":"2016","unstructured":"Iyer, S.R., Valencia, A.P., Hern\u00e1ndez-Ochoa, E.O. & Lovering, R.M. In vivo assessment of muscle contractility in animal studies. Methods Mol. Biol. 1460, 293\u2013307 (2016).","journal-title":"Methods Mol. Biol."},{"key":"BFnm4367_CR23","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/978-1-4939-3810-0_1","volume":"1460","author":"JA Call","year":"2016","unstructured":"Call, J.A. & Lowe, D.A. Eccentric contraction-induced muscle injury: reproducible, quantitative, physiological models to impair skeletal muscle's capacity to generate force. Methods Mol. Biol. 1460, 3\u201318 (2016).","journal-title":"Methods Mol. Biol."},{"key":"BFnm4367_CR24","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1038\/nbt.3290","volume":"33","author":"A Hendel","year":"2015","unstructured":"Hendel, A. et al. Chemically modified guide RNAs enhance CRISPR-Cas genome editing in human primary cells. Nat. Biotechnol. 33, 985\u2013989 (2015).","journal-title":"Nat. Biotechnol."},{"key":"BFnm4367_CR25","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1038\/nbt.3117","volume":"33","author":"SQ Tsai","year":"2015","unstructured":"Tsai, S.Q. et al. GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases. Nat. Biotechnol. 33, 187\u2013197 (2015).","journal-title":"Nat. Biotechnol."},{"key":"BFnm4367_CR26","doi-asserted-by":"publisher","first-page":"950","DOI":"10.1016\/j.cell.2016.01.039","volume":"164","author":"H Hirano","year":"2016","unstructured":"Hirano, H. et al. Structure and engineering of Francisella novicida Cas9. Cell 164, 950\u2013961 (2016).","journal-title":"Cell"},{"key":"BFnm4367_CR27","doi-asserted-by":"publisher","first-page":"14500","DOI":"10.1038\/ncomms14500","volume":"8","author":"E Kim","year":"2017","unstructured":"Kim, E. et al. In vivo genome editing with a small Cas9 orthologue derived from Campylobacter jejuni. Nat. Commun. 8, 14500 (2017).","journal-title":"Nat. Commun."},{"key":"BFnm4367_CR28","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.1038\/nbt.3404","volume":"33","author":"BP Kleinstiver","year":"2015","unstructured":"Kleinstiver, B.P. et al. Broadening the targeting range of Staphylococcus aureus CRISPR-Cas9 by modifying PAM recognition. Nat. Biotechnol. 33, 1293\u20131298 (2015).","journal-title":"Nat. Biotechnol."},{"key":"BFnm4367_CR29","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1038\/nature14592","volume":"523","author":"BP Kleinstiver","year":"2015","unstructured":"Kleinstiver, B.P. et al. Engineered CRISPR-Cas9 nucleases with altered PAM specificities. Nature 523, 481\u2013485 (2015).","journal-title":"Nature"},{"key":"BFnm4367_CR30","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1089\/1066527041410418","volume":"11","author":"G Yeo","year":"2004","unstructured":"Yeo, G. & Burge, C.B. Maximum entropy modeling of short sequence motifs with applications to RNA splicing signals. J. Comput. Biol. 11, 377\u2013394 (2004).","journal-title":"J. Comput. Biol."},{"key":"BFnm4367_CR31","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.1101\/gad.190173.112","volume":"26","author":"X Roca","year":"2012","unstructured":"Roca, X. et al. Widespread recognition of 5\u2032 splice sites by noncanonical base-pairing to U1 snRNA involving bulged nucleotides. Genes Dev. 26, 1098\u20131109 (2012).","journal-title":"Genes Dev."},{"key":"BFnm4367_CR32","doi-asserted-by":"publisher","first-page":"3908","DOI":"10.1093\/nar\/gkw163","volume":"44","author":"J Tan","year":"2016","unstructured":"Tan, J. et al. Noncanonical registers and base pairs in human 5\u2032 splice-site selection. Nucleic Acids Res. 44, 3908\u20133921 (2016).","journal-title":"Nucleic Acids Res."},{"key":"BFnm4367_CR33","doi-asserted-by":"publisher","first-page":"1462","DOI":"10.1096\/fj.11-191189","volume":"26","author":"DU Kemaladewi","year":"2012","unstructured":"Kemaladewi, D.U. et al. Cell-type specific regulation of myostatin signaling. FASEB J. 26, 1462\u20131472 (2012).","journal-title":"FASEB J."},{"key":"BFnm4367_CR34","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/S0960-8966(99)00056-5","volume":"10","author":"JT Vilquin","year":"2000","unstructured":"Vilquin, J.T. et al. Identification of homozygous and heterozygous dy2J mice by PCR. Neuromuscul. Disord. 10, 59\u201362 (2000).","journal-title":"Neuromuscul. Disord."},{"key":"BFnm4367_CR35","doi-asserted-by":"publisher","first-page":"1262","DOI":"10.1016\/j.cell.2014.05.010","volume":"157","author":"PD Hsu","year":"2014","unstructured":"Hsu, P.D., Lander, E.S. & Zhang, F. Development and applications of CRISPR-Cas9 for genome engineering. Cell 157, 1262\u20131278 (2014).","journal-title":"Cell"},{"key":"BFnm4367_CR36","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.ajhg.2015.11.012","volume":"98","author":"D Wojtal","year":"2016","unstructured":"Wojtal, D. et al. Spell checking nature: versatility of CRISPR\/Cas9 for developing treatments for inherited disorders. Am. J. Hum. Genet. 98, 90\u2013101 (2016).","journal-title":"Am. J. Hum. Genet."},{"key":"BFnm4367_CR37","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1126\/science.1231143","volume":"339","author":"L Cong","year":"2013","unstructured":"Cong, L. et al. Multiplex genome engineering using CRISPR\/Cas systems. Science 339, 819\u2013823 (2013).","journal-title":"Science"},{"key":"BFnm4367_CR38","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1038\/nmeth.2649","volume":"10","author":"P Mali","year":"2013","unstructured":"Mali, P., Esvelt, K.M. & Church, G.M. Cas9 as a versatile tool for engineering biology. Nat. Methods 10, 957\u2013963 (2013).","journal-title":"Nat. Methods"},{"key":"BFnm4367_CR39","doi-asserted-by":"publisher","first-page":"13534","DOI":"10.1093\/nar\/gku1206","volume":"42","author":"X Jian","year":"2014","unstructured":"Jian, X., Boerwinkle, E. & Liu, X. In silico prediction of splice-altering single nucleotide variants in the human genome. Nucleic Acids Res. 42, 13534\u201313544 (2014).","journal-title":"Nucleic Acids Res."},{"key":"BFnm4367_CR40","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1038\/nature14539","volume":"521","author":"Y LeCun","year":"2015","unstructured":"LeCun, Y., Bengio, Y. & Hinton, G. Deep learning. Nature 521, 436\u2013444 (2015).","journal-title":"Nature"}],"container-title":["Nature Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nm.4367.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nm.4367","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/doifinder\/10.1038\/nm.4367","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"http:\/\/www.nature.com\/articles\/nm.4367.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T19:02:54Z","timestamp":1684436574000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nm.4367"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,7,17]]},"references-count":40,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2017,8]]}},"alternative-id":["BFnm4367"],"URL":"https:\/\/doi.org\/10.1038\/nm.4367","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.727815117.793540050","asserted-by":"object"}]},"ISSN":["1078-8956","1546-170X"],"issn-type":[{"value":"1078-8956","type":"print"},{"value":"1546-170X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,7,17]]},"assertion":[{"value":"16 November 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 June 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 July 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}