Prime editing corrects the dilated cardiomyopathy causing RBM20-P633L-mutation in human cardiomyocytes.

ABSTRACT: Prime editing (PE) is an innovative next-generation gene editing tool that has therapeutic potential in post-mitotic organs, such as the human heart. However, its applicability and efficiency in non-proliferating cells, e.g., human cardiomyocytes, is not yet established. Here, we apply PE directly in cardiomyocytes differentiated from human induced pluripotent stem cells (hi-CMs) carrying dilated-cardiomyopathy-causing mutations. A target array (TA) containing the mutations LMNA^K117fs (348-349insG), RBM20^P633L (c.1898 C>T), and RBM20^R634Q (c.1901 G>A) in the safe-harbor locus AAVS1 in HEK293T cells served as a screening platform for prime editing gRNAs (pegRNAs). The pegRNA screen yielded a set of efficient pegRNAs targeting the respective mutations. Using

SUBMITTER: Roman A 

PROVIDER: S-EPMC12590231 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature