Ablation of CaMKIIδ oxidation by CRISPR-Cas9 base editing as a therapy for cardiac disease

Authors: Simon Lebek, Francesco Chemello, Xurde M. Caravia, Wei Tan, Hui Li, Kenian Chen, Lin Xu, Ning Liu, Rhonda Bassel-Duby, Eric N. Olson

Published: 2023-01-12

DOI: 10.1126/science.ade1105

Source: Full article


Abstract

CRISPR-Cas9 gene editing is emerging as a prospective therapy for genomic mutations. However, current editing approaches are directed primarily toward relatively small cohorts of patients with specific mutations. Here, we describe a cardioprotective strategy potentially applicable to a broad range of patients with heart disease. We used base editing to ablate the oxidative activation sites of CaMKIIδ, a primary driver of cardiac disease. We show in cardiomyocytes derived from human induced pluripotent stem cells that editing the