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Mutations in the\n                    <jats:italic>DYSF<\/jats:italic>\n                    gene cause a panoply of genetic muscular dystrophies. We targeted a frequent loss-of-function,\n                    <jats:italic>DYSF<\/jats:italic>\n                    exon 44, founder frameshift mutation with mRNA-mediated delivery of SpCas9 in combination with a mutation-specific sgRNA to primary muscle stem cells from two homozygous patients. We observed a consistent &gt;60% exon 44 re-framing, rescuing a full-length and functional dysferlin protein. A new mouse model harboring a humanized\n                    <jats:italic>Dysf<\/jats:italic>\n                    exon 44 with the founder mutation, hEx44mut, recapitulates the patients\u2019 phenotype and an identical re-framing outcome in primary muscle stem cells. Finally, gene-edited murine primary muscle stem-cells are able to regenerate muscle and rescue dysferlin when transplanted back into hEx44mut hosts. These findings are the first to show that a CRISPR-mediated therapy can ameliorate dysferlin deficiency. We suggest that gene-edited primary muscle stem cells could exhibit utility, not only in treating dysferlin deficiency syndromes, but also perhaps other forms of muscular dystrophy.\n                  <\/jats:p>","DOI":"10.1038\/s41467-024-55086-0","type":"journal-article","created":{"date-parts":[[2025,1,2]],"date-time":"2025-01-02T20:15:19Z","timestamp":1735848919000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Gene-editing in patient and humanized-mice primary muscle stem cells rescues dysferlin expression in dysferlin-deficient muscular dystrophy"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8128-7845","authenticated-orcid":false,"given":"Helena","family":"Escobar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Di Francescantonio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Smirnova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5400-9938","authenticated-orcid":false,"given":"Robin","family":"Graf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3525-8859","authenticated-orcid":false,"given":"Stefanie","family":"M\u00fcthel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3673-4244","authenticated-orcid":false,"given":"Andreas","family":"Marg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexej","family":"Zhogov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Supriya","family":"Krishna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Metzler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mina","family":"Petkova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6190-1414","authenticated-orcid":false,"given":"Oliver","family":"Daumke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1694-9803","authenticated-orcid":false,"given":"Ralf","family":"K\u00fchn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0155-1117","authenticated-orcid":false,"given":"Simone","family":"Spuler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,2]]},"reference":[{"key":"55086_CR1","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1038\/1689","volume":"20","author":"R Bashir","year":"1998","unstructured":"Bashir, R. et al. 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