Restoration of Osteogenesis by CRISPR/Cas9 Genome Editing of the Mutated COL1A1 Gene in Osteogenesis Imperfecta

被引：22

作者：

Jung, Hyerin ^{[1
,2
]}

Rim, Yeri Alice ^{[1
,2
]}

Park, Narae ^{[1
,2
]}

Nam, Yoojun ^{[3
]}

Ju, Ji Hyeon ^{[1
,2
,3
,4
]}

机构：

[1] Catholic Univ Korea, Seoul St Marys Hosp, CiSTEM Lab, Convergent Res Consortium Immunol Dis,Coll Med, 222 Banpo Daero, Seoul 06591, South Korea

[2] Catholic Univ Korea, Coll Med, Catholic iPSC Res Ctr, Seoul 137701, South Korea

[3] YiPSCELL Inc, 39 Banpo Daero, Seoul 06579, South Korea

[4] Catholic Univ Korea, Seoul St Marys Hosp, Coll Med, Div Rheumatol,Dept Internal Med, 222 Banpo Daero, Seoul 06281, South Korea

来源：

JOURNAL OF CLINICAL MEDICINE | 2021年 / 10卷 / 14期

基金：

新加坡国家研究基金会;

关键词：

osteogenesis imperfecta; osteoblast differentiation; induced pluripotent stem cell; gene editing; I COLLAGEN; STEM-CELLS; BONE; MUTATIONS; RNA; CRISPR-CAS9; PROCOLLAGEN; GENERATION; SITES; CHAIN;

D O I：

10.3390/jcm10143141

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 cells (iPSCs) from OI patient-derived blood cells harboring a mutation in the COL1A1 gene. Osteoblast (OB) differentiated from OI-iPSCs showed abnormally decreased levels of type I collagen and osteogenic differentiation ability. Gene correction of the COL1A1 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.

引用

页数：19

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