Targeted gene correction and functional recovery in achondroplasia patient-derived iPSCs

Stem Cell Research & Therapy

Yundong Li¹  Wenyuan Wang¹  Mingfeng Guan¹  Fang Luo¹  Huan Zou¹  Yiren Qin² 

[1] Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 201210, Shanghai, China;Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 201210, Shanghai, China;2State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 200127, Shanghai, China;

关键词: Achondroplasia;    iPSCs;    Gene correction;    CRISPR-Cas9;   

DOI  :  10.1186/s13287-021-02555-8

来源: Springer

【 摘 要 】

BackgroundAchondroplasia (ACH) is the most common genetic form of dwarfism and belongs to dominant monogenic disorder caused by a gain-of-function point mutation in the transmembrane region of FGFR3. There are no effective treatments for ACH. Stem cells and gene-editing technology provide us with effective methods and ideas for ACH research and treatment.MethodsWe generated non-integrated iPSCs from an ACH girl’s skin and an ACH boy’s urine by Sendai virus. The mutation of ACH iPSCs was precisely corrected by CRISPR-Cas9.ResultsChondrogenic differentiation ability of ACH iPSCs was confined compared with that of healthy iPSCs. Chondrogenic differentiation ability of corrected ACH iPSCs could be restored. These corrected iPSCs displayed pluripotency, maintained normal karyotype, and demonstrated none of off-target indels.ConclusionsThis study may provide an important theoretical and experimental basis for the ACH research and treatment.

【 授权许可】

CC BY