{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:36:07Z","timestamp":1790314567660,"version":"4.1.0"},"reference-count":35,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T00:00:00Z","timestamp":1670457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Foundation Gisela Krebs"},{"name":"the Deutsche Muskelschwundhilfe"},{"name":"the MightyMaje initiative"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>LMNA-related muscular dystrophy is an autosomal-dominant progressive disorder caused by mutations in LMNA. LMNA missense mutations are becoming correctable with CRISPR\/Cas9-derived tools. Evaluating the functional recovery of LMNA after gene editing bears challenges as there is no reported direct loss of function of lamin A\/C proteins in patient-derived cells. The proteins encoded by LMNA are lamins A\/C, important ubiquitous nuclear envelope proteins but absent in pluripotent stem cells. We induced lamin A\/C expression in induced pluripotent stem cells (iPSCs) of two patients with LMNA-related muscular dystrophy, NM_170707.4 (LMNA): c.1366A &gt; G, p.(Asn456Asp) and c.1494G &gt; T, p.(Trp498Cys), using a short three-day, serum-induced differentiation protocol and analyzed expression profiles of co-regulated genes, examples being COL1A2 and S100A6. We then performed precise gene editing of LMNA c.1366A &gt; G using the near-PAMless (PAM: protospacer-adjacent motif) cytosine base editor. We show that the mutation can be repaired to 100% efficiency in individual iPSC clones. The fast differentiation protocol provided a functional readout and demonstrated increased lamin A\/C expression as well as normalized expression of co-regulated genes. Collectively, our findings demonstrate the power of CRISPR\/Cas9-mediated gene correction and effective outcome measures in a disease with, so far, little perspective on therapies.<\/jats:p>","DOI":"10.3390\/ijms232415525","type":"journal-article","created":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T01:44:31Z","timestamp":1670463871000},"page":"15525","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["LMNA Co-Regulated Gene Expression as a Suitable Readout after Precise Gene Correction"],"prefix":"10.3390","volume":"23","author":[{"given":"Haicui","family":"Wang","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\u2014Universit\u00e4tsmedizin Berlin, 13125 Berlin, Germany"},{"name":"Max Delbr\u00fcck Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany"},{"name":"Berlin Institute of Health, Charit\u00e9 Universit\u00e4tsmedizin Berlin, 13125 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Krause","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\u2014Universit\u00e4tsmedizin Berlin, 13125 Berlin, Germany"},{"name":"Max Delbr\u00fcck Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany"},{"name":"Berlin Institute of Health, Charit\u00e9 Universit\u00e4tsmedizin Berlin, 13125 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8128-7845","authenticated-orcid":false,"given":"Helena","family":"Escobar","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\u2014Universit\u00e4tsmedizin Berlin, 13125 Berlin, Germany"},{"name":"Max Delbr\u00fcck Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany"},{"name":"Berlin Institute of Health, Charit\u00e9 Universit\u00e4tsmedizin Berlin, 13125 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\u2014Universit\u00e4tsmedizin Berlin, 13125 Berlin, Germany"},{"name":"Max Delbr\u00fcck Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany"},{"name":"Berlin Institute of Health, Charit\u00e9 Universit\u00e4tsmedizin Berlin, 13125 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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\u2014Universit\u00e4tsmedizin Berlin, 13125 Berlin, Germany"},{"name":"Max Delbr\u00fcck Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany"},{"name":"Berlin Institute of Health, Charit\u00e9 Universit\u00e4tsmedizin Berlin, 13125 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0155-1117","authenticated-orcid":false,"given":"Simone","family":"Spuler","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\u2014Universit\u00e4tsmedizin Berlin, 13125 Berlin, Germany"},{"name":"Max Delbr\u00fcck Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany"},{"name":"Berlin Institute of Health, Charit\u00e9 Universit\u00e4tsmedizin Berlin, 13125 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Donnaloja, F., Carnevali, F., Jacchetti, E., and Raimondi, M.T. 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