Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, 201210, 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, Shanghai, 200127, China.
Stem Cell Res Ther. 2021 Aug 28;12(1):485. doi: 10.1186/s13287-021-02555-8.
Achondroplasia (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.
We 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.
Chondrogenic 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.
This study may provide an important theoretical and experimental basis for the ACH research and treatment.
软骨发育不全症（ACH）是最常见的遗传性侏儒症，属于 FGFR3 跨膜区功能获得性点突变引起的显性单基因疾病。目前尚无有效的 ACH 治疗方法。干细胞和基因编辑技术为 ACH 的研究和治疗提供了有效的方法和思路。
我们利用 Sendai 病毒从一名 ACH 女孩的皮肤和一名 ACH 男孩的尿液中生成非整合 iPSCs。通过 CRISPR-Cas9 对 ACH iPSCs 的突变进行精确校正。
ACH iPSCs 的软骨分化能力受到限制，与健康 iPSCs 相比。校正后的 ACH iPSCs 的软骨分化能力可以恢复。这些校正后的 iPSCs 表现出多能性，保持正常核型，并且没有脱靶插入缺失。
本研究可能为 ACH 的研究和治疗提供重要的理论和实验基础。
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