{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:35:20Z","timestamp":1787027720564,"version":"build-2736575974"},"reference-count":42,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T00:00:00Z","timestamp":1730851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Million Dollar Bike Ride Award 2018\u2014Orphan Disease Center, Pennsylvania University (UPENN) (Principal investigator, AR)","award":["CUP B93D21010860004"],"award-info":[{"award-number":["CUP B93D21010860004"]}]},{"name":"Million Dollar Bike Ride Award 2018\u2014Orphan Disease Center, Pennsylvania University (UPENN) (Principal investigator, AR)","award":["20223WFJJ3"],"award-info":[{"award-number":["20223WFJJ3"]}]},{"name":"European Union\u2014Next Generation EU, Mission 4, Component 2","award":["CUP B93D21010860004"],"award-info":[{"award-number":["CUP B93D21010860004"]}]},{"name":"European Union\u2014Next Generation EU, Mission 4, Component 2","award":["20223WFJJ3"],"award-info":[{"award-number":["20223WFJJ3"]}]},{"name":"PIANO NAZIONALE DI RIPRESA E RESILIENZA (PNRR) Missione 4 \u201cIstruzione e Ricerca\u201d\u2014Componente C2 Investimento 1.1","award":["CUP B93D21010860004"],"award-info":[{"award-number":["CUP B93D21010860004"]}]},{"name":"PIANO NAZIONALE DI RIPRESA E RESILIENZA (PNRR) Missione 4 \u201cIstruzione e Ricerca\u201d\u2014Componente C2 Investimento 1.1","award":["20223WFJJ3"],"award-info":[{"award-number":["20223WFJJ3"]}]},{"name":"Fondo per il Programma Nazionale di Ricerca e Progetti di Rilevante Interesse Nazionale (PRIN)","award":["CUP B93D21010860004"],"award-info":[{"award-number":["CUP B93D21010860004"]}]},{"name":"Fondo per il Programma Nazionale di Ricerca e Progetti di Rilevante Interesse Nazionale (PRIN)","award":["20223WFJJ3"],"award-info":[{"award-number":["20223WFJJ3"]}]},{"name":"Umberto Veronesi Foundation (Italy)","award":["CUP B93D21010860004"],"award-info":[{"award-number":["CUP B93D21010860004"]}]},{"name":"Umberto Veronesi Foundation (Italy)","award":["20223WFJJ3"],"award-info":[{"award-number":["20223WFJJ3"]}]},{"name":"European Reference Network for Neuromuscular diseases (ERN Euro-NMD, AF and GF representatives)","award":["CUP B93D21010860004"],"award-info":[{"award-number":["CUP B93D21010860004"]}]},{"name":"European Reference Network for Neuromuscular diseases (ERN Euro-NMD, AF and GF representatives)","award":["20223WFJJ3"],"award-info":[{"award-number":["20223WFJJ3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Collagen VI is an essential component of the extracellular matrix (ECM) composed by \u03b11, \u03b12 and \u03b13 chains and encoded by COL6A1, COL6A2 and COL6A3 genes. Dominant negative pathogenic variants in COL6A genes result in defects in collagen VI protein and are implicated in the pathogenesis of muscular diseases, including Ullrich congenital muscular dystrophy (UCMD). Here, we designed a CRISPR genome editing strategy to tackle a dominant heterozygous deletion c.824_838del in exon 9 of the COL6A1 gene, causing a lack of secreted collagen VI in a patient\u2019s dermal fibroblasts. The evaluation of efficiency and specificity of gene editing in treating patient\u2019s fibroblasts revealed the 32% efficiency of editing the mutated allele but negligible editing of the wild-type allele. CRISPR-treated UCMD skin fibroblasts rescued the secretion of collagen VI in the ECM, which restored the ultrastructure of the collagen VI microfibril network. By using normal melanocytes as surrogates of muscle cells, we found that collagen VI secreted by the corrected patient\u2019s skin fibroblasts recovered the anchorage to the cell surface, pointing to a functional improvement of the protein properties. These results support the application of the CRISPR editing approach to knock out COL6A1 mutated alleles and rescue the UCMD phenotype in patient-derived fibroblasts.<\/jats:p>","DOI":"10.3390\/biom14111412","type":"journal-article","created":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T06:27:39Z","timestamp":1730874459000},"page":"1412","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Restored Collagen VI Microfilaments Network in the Extracellular Matrix of CRISPR-Edited Ullrich Congenital Muscular Dystrophy Fibroblasts"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6599-7193","authenticated-orcid":false,"given":"Daniela","family":"Benati","sequence":"first","affiliation":[{"name":"Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Cattin","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4926-0411","authenticated-orcid":false,"given":"Federico","family":"Corradi","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommaso","family":"Ferrari","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Pedrazzoli","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarissa","family":"Patrizi","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1163-3466","authenticated-orcid":false,"given":"Matteo","family":"Marchionni","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2541-5419","authenticated-orcid":false,"given":"Roberto","family":"Bertorelli","sequence":"additional","affiliation":[{"name":"Next Generation Sequencing Core Facility Department of Cellular, Computational and Integrative Biomedicine\u2014CIBIO LaBSSAH, University of Trento, 38122 Trento, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9791-5316","authenticated-orcid":false,"given":"Veronica","family":"De Sanctis","sequence":"additional","affiliation":[{"name":"Next Generation Sequencing Core Facility Department of Cellular, Computational and Integrative Biomedicine\u2014CIBIO LaBSSAH, University of Trento, 38122 Trento, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciano","family":"Merlini","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Science, DIBINEM, University of Bologna, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8385-9870","authenticated-orcid":false,"given":"Alessandra","family":"Ferlini","sequence":"additional","affiliation":[{"name":"Section of Medical Genetics, Department of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy"},{"name":"Unit of Medical Genetics, Department of Mother and Child, University Hospital S. Anna Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Sabatelli","sequence":"additional","affiliation":[{"name":"CNR-Institute of Molecular Genetics, 40136 Bologna, Italy"},{"name":"IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9551-057X","authenticated-orcid":false,"given":"Francesca","family":"Gualandi","sequence":"additional","affiliation":[{"name":"Unit of Medical Genetics, Department of Mother and Child, University Hospital S. Anna Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3467-1094","authenticated-orcid":false,"given":"Alessandra","family":"Recchia","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1196\/annals.1427.009","article-title":"Dysfunction of mitochondria and sarcoplasmic reticulum in the pathogenesis of collagen VI muscular dystrophies","volume":"1147","author":"Bernardi","year":"2008","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_2","first-page":"3525","article-title":"Collagen VI at a glance","volume":"128","author":"Cescon","year":"2015","journal-title":"J. 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