Restoration of Osteogenesis by CRISPR/Cas9 Genome Editing of the Mutated COL1A1 Gene in Osteogenesis Imperfecta
30 Pages Posted: 28 Jan 2019More...
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 COL1A1 or COL1A2. Current strategies for treating OI are not curative. In this study, we generated induced pluripotent stem cell (iPSCs) from OI patients harboring a mutation in the COL1A1 gene. OI-iPSCs exhibited abnormal collagen triple-helix structure and defective mineralization during osteogenesis in vitro. Gene-corrected OI-iPSCs exhibited recovery from the "untwisted" to "twisted" collagen triple-helix structure. In addition, gene correction restored osteogenic potential.
Funding Statement: This work was supported by a grant from the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare and Family Affairs, Republic of Korea (H16C2177, H18C1178).
Declaration of Interests: The authors declare no competing interests.
Ethics Approval Statement: All procedures involving animals were performed in accordance with the Laboratory Animals Welfare Act, the Guide for the Care and Use of Laboratory Animals, and the Guidelines and Policies for Rodent Experimentation provided by the Institutional Animal Care and Use Committee of the School of Medicine of The Catholic University of Korea. The study protocol was approved by the Institutional Review Board of The Catholic University of Korea (CUMC-2016-0291-02) from the Catholic iPSCs Center.
Keywords: osteogenesis imperfecta; induced pluripotent stem cells; COL1A1; collagen; triplehelix; CRISPR/Cas9; osteogenic differentiation
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