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

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 girls skin and an ACH boys 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.