Restoration of Osteogenesis by CRISPR/Cas9 Genome Editing of the Mutated <i>COL1A1</i> Gene in Osteogenesis Imperfecta
Osteogenesis imperfecta (OI) is a genetic disease characterized by bone fragility and repeated fractures. The bone fragility associated with OI is caused by a defect in collagen formation due to mutation of <i>COL1A1</i> or <i>COL1A2</i>. Current strategies for treating OI ar...
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| Format: | Article |
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MDPI AG
2021-07-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/10/14/3141 |
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| author | Hyerin Jung Yeri Alice Rim Narae Park Yoojun Nam Ji Hyeon Ju |
| author_facet | Hyerin Jung Yeri Alice Rim Narae Park Yoojun Nam Ji Hyeon Ju |
| author_sort | Hyerin Jung |
| collection | DOAJ |
| description | Osteogenesis imperfecta (OI) is a genetic disease characterized by bone fragility and repeated fractures. The bone fragility associated with OI is caused by a defect in collagen formation due to mutation of <i>COL1A1</i> or <i>COL1A2</i>. Current strategies for treating OI are not curative. In this study, we generated induced pluripotent stem cells (iPSCs) from OI patient-derived blood cells harboring a mutation in the <i>COL1A1</i> gene. Osteoblast (OB) differentiated from OI-iPSCs showed abnormally decreased levels of type I collagen and osteogenic differentiation ability. Gene correction of the <i>COL1A1</i> gene using CRISPR/Cas9 recovered the decreased type I collagen expression in OBs differentiated from OI-iPSCs. The osteogenic potential of OI-iPSCs was also recovered by the gene correction. This study suggests a new possibility of treatment and in vitro disease modeling using patient-derived iPSCs and gene editing with CRISPR/Cas9. |
| first_indexed | 2024-03-10T09:34:56Z |
| format | Article |
| id | doaj.art-025385d8e49f457999db1a8d4495600d |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-10T09:34:56Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-025385d8e49f457999db1a8d4495600d2023-11-22T04:07:19ZengMDPI AGJournal of Clinical Medicine2077-03832021-07-011014314110.3390/jcm10143141Restoration of Osteogenesis by CRISPR/Cas9 Genome Editing of the Mutated <i>COL1A1</i> Gene in Osteogenesis ImperfectaHyerin Jung0Yeri Alice Rim1Narae Park2Yoojun Nam3Ji Hyeon Ju4CiSTEM Laboratory, Convergent Research Consortium for Immunologic Disease, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, KoreaCiSTEM Laboratory, Convergent Research Consortium for Immunologic Disease, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, KoreaCiSTEM Laboratory, Convergent Research Consortium for Immunologic Disease, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, KoreaYiPSCELL, Inc., 39 Banpo-daero, Seocho-gu, Seoul 06579, KoreaCiSTEM Laboratory, Convergent Research Consortium for Immunologic Disease, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, KoreaOsteogenesis imperfecta (OI) is a genetic disease characterized by bone fragility and repeated fractures. The bone fragility associated with OI is caused by a defect in collagen formation due to mutation of <i>COL1A1</i> or <i>COL1A2</i>. Current strategies for treating OI are not curative. In this study, we generated induced pluripotent stem cells (iPSCs) from OI patient-derived blood cells harboring a mutation in the <i>COL1A1</i> gene. Osteoblast (OB) differentiated from OI-iPSCs showed abnormally decreased levels of type I collagen and osteogenic differentiation ability. Gene correction of the <i>COL1A1</i> gene using CRISPR/Cas9 recovered the decreased type I collagen expression in OBs differentiated from OI-iPSCs. The osteogenic potential of OI-iPSCs was also recovered by the gene correction. This study suggests a new possibility of treatment and in vitro disease modeling using patient-derived iPSCs and gene editing with CRISPR/Cas9.https://www.mdpi.com/2077-0383/10/14/3141osteogenesis imperfectaosteoblast differentiationinduced pluripotent stem cell<i>COL1A1</i>gene editing |
| spellingShingle | Hyerin Jung Yeri Alice Rim Narae Park Yoojun Nam Ji Hyeon Ju Restoration of Osteogenesis by CRISPR/Cas9 Genome Editing of the Mutated <i>COL1A1</i> Gene in Osteogenesis Imperfecta Journal of Clinical Medicine osteogenesis imperfecta osteoblast differentiation induced pluripotent stem cell <i>COL1A1</i> gene editing |
| title | Restoration of Osteogenesis by CRISPR/Cas9 Genome Editing of the Mutated <i>COL1A1</i> Gene in Osteogenesis Imperfecta |
| title_full | Restoration of Osteogenesis by CRISPR/Cas9 Genome Editing of the Mutated <i>COL1A1</i> Gene in Osteogenesis Imperfecta |
| title_fullStr | Restoration of Osteogenesis by CRISPR/Cas9 Genome Editing of the Mutated <i>COL1A1</i> Gene in Osteogenesis Imperfecta |
| title_full_unstemmed | Restoration of Osteogenesis by CRISPR/Cas9 Genome Editing of the Mutated <i>COL1A1</i> Gene in Osteogenesis Imperfecta |
| title_short | Restoration of Osteogenesis by CRISPR/Cas9 Genome Editing of the Mutated <i>COL1A1</i> Gene in Osteogenesis Imperfecta |
| title_sort | restoration of osteogenesis by crispr cas9 genome editing of the mutated i col1a1 i gene in osteogenesis imperfecta |
| topic | osteogenesis imperfecta osteoblast differentiation induced pluripotent stem cell <i>COL1A1</i> gene editing |
| url | https://www.mdpi.com/2077-0383/10/14/3141 |
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