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Purpose: To investigate the pathological mechanisms underlying this cardiomyopathy and to search for novel pharmaceutical and genetic therapeutic modalities, we generated induced Pluripotent Stem Cells-derived cardiomyocytes (iPSC-CMs) from a patient with WPW, atrioventricular block and cardiomyopathy caused by a R302Q mutation in PRKAG2 gene. To this end, we investigated whether:(1) the cellular abnormalities of the mutated iPSC-CMs are compatible with key clinical symptoms;(2) correcting the mutation by means of CRISPR/Cas9 will confer normal function to the otherwise diseased cardiomyocytes.

Results: Reprogramming the patient's skin fibroblasts resulted in iPSCs colonies expressing the R302Q mutation. Using the CRISPR/Cas9 technology we successfully corrected the mutated chromosomal locus, thereby generating an isogenic control iPSC clone that carries homogenous wild-type …