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Biosci. (Landmark Ed)"],"abstract":"<jats:p>Background: Osteopetrosis represents a rare genetic disease with a wide range of clinical and genetic heterogeneity, which results from osteoclast failure. Although up to 10 genes have been identified to be related with osteopetrosis, the pathogenesis of osteopetrosis remains foggy. Disease-specific induced pluripotent stem cells (iPSCs) and gene-corrected disease specific iPSCs provide a platform to generate attractive in vitro disease cell models and isogenic control cellular models respectively. The purpose of this study is to rescue the disease causative mutation in osteopetrosis specific induced pluripotent stem cells and provide isogenic control cellular models. Methods: Based on our previously established osteopetrosis-specific iPSCs (ADO2-iPSCs), we repaired the point mutation R286W of the CLCN7 gene in ADO2-iPSCs by the clustered regularly interspaced short palindromic repeats (CRISPR)\/CRISPR-associated protein 9 (Cas9) mediated homologous recombination. Results: The obtained gene corrected ADO2-iPSCs (GC-ADO2-iPSCs) were characterized in terms of hESC-like morphology, a normal karyotype, expression of pluripotency markers, homozygous repaired sequence of CLCN7 gene, and the ability to differentiate into cells of three germ layers. Conclusions: We successfully corrected the point mutation R286W of the CLCN7 gene in ADO2-iPSCs. This isogenic iPSC line is an ideal control cell model for deciphering the pathogenesis of osteopetrosis in future studies.<\/jats:p>","DOI":"10.31083\/j.fbl2806131","type":"journal-article","created":{"date-parts":[[2023,7,3]],"date-time":"2023-07-03T05:36:35Z","timestamp":1688362595000},"source":"Crossref","is-referenced-by-count":4,"title":["CRISPR\/Cas9-Mediated Gene Correction in Osteopetrosis Patient-Derived iPSCs"],"prefix":"10.31083","volume":"28","author":[{"given":"Dandan","family":"Li","sequence":"first","affiliation":[{"name":"Clinical Medical Research Center, The Second Clinical Medical College of Jinan University (Shenzhen People's Hospital), 518020 Shenzhen, Guangdong, China"},{"name":"Institute of Nephrology and Blood Purification, The First Affiliated Hospital, Jinan University, 510632 Guangzhou, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minglin","family":"Ou","sequence":"first","affiliation":[{"name":"Clinical Medical Research Center, The Second Clinical Medical College of Jinan University (Shenzhen People's Hospital), 518020 Shenzhen, Guangdong, China"},{"name":"Central Laboratory, Guangxi Health Commission Key Laboratory of Glucose and Lipid Metabolism Disorders, The Second Affiliated Hospital of Guilin Medical University, 541001 Guilin, Guangxi, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Zhang","sequence":"first","affiliation":[{"name":"Clinical Medical Research Center, The Second Clinical Medical College of Jinan University (Shenzhen People's Hospital), 518020 Shenzhen, Guangdong, China"},{"name":"Institute of Nephrology and Blood Purification, The First Affiliated Hospital, Jinan University, 510632 Guangzhou, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Luo","sequence":"first","affiliation":[{"name":"Clinical Medical Research Center, The Second Clinical Medical College of Jinan University (Shenzhen People's Hospital), 518020 Shenzhen, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanxia","family":"Cai","sequence":"first","affiliation":[{"name":"Clinical Medical Research Center, The Second Clinical Medical College of Jinan University (Shenzhen People's Hospital), 518020 Shenzhen, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chune","family":"Mo","sequence":"first","affiliation":[{"name":"Central Laboratory, Guangxi Health Commission Key Laboratory of Glucose and Lipid Metabolism Disorders, The Second Affiliated Hospital of Guilin Medical University, 541001 Guilin, Guangxi, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenken","family":"Liang","sequence":"first","affiliation":[{"name":"Central Laboratory, Guangxi Health Commission Key Laboratory of Glucose and Lipid Metabolism Disorders, The Second Affiliated Hospital of Guilin Medical University, 541001 Guilin, Guangxi, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guandong","family":"Dai","sequence":"first","affiliation":[{"name":"Clinical Lab of Shenzhen Pingshan People's Hospital, Shenzhen Pingshan People's Hospital, 518118 Shenzhen, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lianghong","family":"Yin","sequence":"first","affiliation":[{"name":"Institute of Nephrology and Blood Purification, The First Affiliated Hospital, Jinan University, 510632 Guangzhou, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Zhu","sequence":"first","affiliation":[{"name":"Clinical Lab of Shenzhen Pingshan People's Hospital, Shenzhen Pingshan People's Hospital, 518118 Shenzhen, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donge","family":"Tang","sequence":"first","affiliation":[{"name":"Clinical Medical Research Center, The Second Clinical Medical College of Jinan University (Shenzhen People's Hospital), 518020 Shenzhen, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Dai","sequence":"first","affiliation":[{"name":"Clinical Medical Research Center, The Second Clinical Medical College of Jinan University (Shenzhen People's Hospital), 518020 Shenzhen, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"16242","published-online":{"date-parts":[[2023,6,30]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","unstructured":"Sobacchi C, Schulz A, Coxon FP, Villa A, Helfrich MH. 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