Precise genomic editing of pathogenic mutations in RBM20 rescues dilated cardiomyopathy.

ABSTRACT: Mutations in RNA binding motif protein 20 (RBM20) are a common cause of familial dilated cardiomyopathy (DCM). Many RBM20 mutations cluster within an arginine/serine-rich (RS-rich) domain, which mediates nuclear localization. These mutations induce RBM20 mis-localization to form aberrant ribonucleoprotein (RNP) granules in the cytoplasm of cardiomyocytes and abnormal alternative splicing of cardiac genes, contributing to DCM. We used adenine base editing (ABE) and prime editing (PE) to correct pathogenic p.R634Q and p.R636S mutations in the RS-rich domain in human isogenic induced pluripotent stem cell (iPSC)-derived cardiomyocytes. Using ABE to correct RBM20^R634Q human iPSCs, we achieved 92% efficiency of A-to-G editing, which normalized alternative splicin

SUBMITTER: Nishiyama T 

PROVIDER: S-EPMC10088465 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature