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

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

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


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 CaMKIId, a primary driver of cardiac disease. We show in cardiomyocytes derived from human induced pluripotent stem cells that editing the CaMKIId gene to eliminate oxidation-sensitive methionine residues confers protection from ischemia/reperfusion (IR) injury. Moreover, CaMKIId editing in mice at the time of IR enables the heart to recover function from otherwise severe damage. CaMKIId gene editing may thus represent a permanent and advanced strategy for heart disease therapy.

Original languageEnglish (US)
Pages (from-to)179-185
Number of pages7
Issue number6628
StatePublished - Jan 13 2023

ASJC Scopus subject areas

  • General


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