Cas13b-mediated RNA targeted therapy alleviates genetic dilated cardiomyopathy in mice

Abstract Background Recent advances in gene editing technology have opened up new avenues for in vivo gene therapy, which holds great promise as a potential treatment method for dilated cardiomyopathy (DCM). The CRISPR-Cas13 system has been shown to be an effective tool for knocking down RNA expression in mammalian cells. Results In this study, we delivered PspCas13b with hTNNT2R141W gRNA into human TNNT2R141W (hTNNT2R141W) transgenic DCM mouse model using adeno-associated virus (AAV), resulting in effective knockdown of hTNNT2R141W transcripts. Cas13b-mediated knockdown significantly increased myofilament sensitivity to Ca2+, improved cardiac function, and reduced myocardial fibrosis in DCM mice. Conclusions These findings suggest that targeting genes through Cas13b represents a promising approach for in vivo gene therapy for genetic diseases caused by aberrant gene expression. Our study provides further evidence of Cas13b's application in genetic disease therapy and paves the way for future applications of genetic therapies for cardiomyopathy.