{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T19:56:20Z","timestamp":1793044580393,"version":"4.5.0"},"reference-count":53,"publisher":"American Society for Clinical Investigation","issue":"10","license":[{"start":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T00:00:00Z","timestamp":1621814400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Gisela Krebs Foundation","award":["Postdoc grant to Helena Escobar"],"award-info":[{"award-number":["Postdoc grant to Helena Escobar"]}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["SP 1152\/12-1"],"award-info":[{"award-number":["SP 1152\/12-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Helmholtz Association","award":["Pre-GoBio"],"award-info":[{"award-number":["Pre-GoBio"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,5,24]]},"abstract":"<jats:p>\n                    Skeletal muscle can regenerate from muscle stem cells and their myogenic precursor cell progeny, myoblasts. However, precise gene editing in human muscle stem cells for autologous cell replacement therapies of untreatable genetic muscle diseases has not yet been reported. Loss-of-function mutations in\n                    <jats:italic>SGCA<\/jats:italic>\n                    , encoding \u03b1-sarcoglycan, cause limb-girdle muscular dystrophy 2D\/R3, an early-onset, severe, and rapidly progressive form of muscular dystrophy affecting both male and female patients. Patients suffer from muscle degeneration and atrophy affecting the limbs, respiratory muscles, and heart. We isolated human muscle stem cells from 2 donors, with the common\n                    <jats:italic>SGCA<\/jats:italic>\n                    c.157G&gt;A mutation affecting the last coding nucleotide of exon 2. We found that c.157G&gt;A is an exonic splicing mutation that induces skipping of 2 coregulated exons. Using adenine base editing, we corrected the mutation in the cells from both donors with &gt; 90% efficiency, thereby rescuing the splicing defect and \u03b1-sarcoglycan expression. Base-edited patient cells regenerated muscle and contributed to the Pax7\n                    <jats:sup>+<\/jats:sup>\n                    satellite cell compartment in vivo in mouse xenografts. Here, we provide the first evidence to our knowledge that autologous gene\u2013repaired human muscle stem cells can be harnessed for cell replacement therapies of muscular dystrophies.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.145994","type":"journal-article","created":{"date-parts":[[2021,4,13]],"date-time":"2021-04-13T12:55:36Z","timestamp":1618318536000},"source":"Crossref","is-referenced-by-count":28,"title":["Base editing repairs an SGCA mutation in human primary muscle stem cells"],"prefix":"10.1172","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8128-7845","authenticated-orcid":true,"given":"Helena","family":"Escobar","sequence":"first","affiliation":[{"name":"Muscle Research Unit, Experimental and Clinical Research Center, a cooperation between the Max-Delbr\u00fcck-Center for Molecular Medicine in the Helmholtz Association and the Charit\u00e9, Universit\u00e4tsmedizin Berlin, Germany."},{"name":"Charit\u00e9 Universit\u00e4tsmedizin Berlin, 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Chemistry and Biochemistry, Laboratory of RNA Biochemistry, Berlin, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janine","family":"Kieshauer","sequence":"additional","affiliation":[{"name":"Muscle Research Unit, Experimental and Clinical Research Center, a cooperation between the Max-Delbr\u00fcck-Center for Molecular Medicine in the Helmholtz Association and the Charit\u00e9, Universit\u00e4tsmedizin Berlin, Germany."},{"name":"Charit\u00e9 Universit\u00e4tsmedizin Berlin, Germany."},{"name":"Max-Delbr\u00fcck-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"M\u00fcthel","sequence":"additional","affiliation":[{"name":"Muscle Research Unit, Experimental and Clinical Research Center, a cooperation between the Max-Delbr\u00fcck-Center for Molecular Medicine in the Helmholtz Association and the Charit\u00e9, Universit\u00e4tsmedizin Berlin, Germany."},{"name":"Charit\u00e9 Universit\u00e4tsmedizin Berlin, Germany."},{"name":"Max-Delbr\u00fcck-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel Garc\u00eda","family":"de Paredes","sequence":"additional","affiliation":[{"name":"Muscle Research Unit, Experimental and Clinical Research Center, a cooperation between the Max-Delbr\u00fcck-Center for Molecular Medicine in the Helmholtz Association and the Charit\u00e9, Universit\u00e4tsmedizin Berlin, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1735-6364","authenticated-orcid":true,"given":"Eric","family":"Metzler","sequence":"additional","affiliation":[{"name":"Muscle Research Unit, Experimental and Clinical Research Center, a cooperation between the Max-Delbr\u00fcck-Center for Molecular Medicine in the Helmholtz Association and the Charit\u00e9, Universit\u00e4tsmedizin 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