Lebek, Simon and Chemello, Francesco and Caravia, Xurde M. and Tan, Wei and Li, Hui and Chen, Kenian and Xu, Lin and Liu, Ning and Bassel-Duby, Rhonda and Olson, Eric N. (2023) Ablation of CaMKIId oxidation by CRISPR-Cas9 base editing as a therapy for cardiac disease. SCIENCE, 379 (6628). pp. 179-185. ISSN 0036-8075, 1095-9203
Full text not available from this repository. (Request a copy)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 CaMKIId, a primary driver of cardiac disease. We show in cardiomyocytes derived from human induced pluripotent stem cells that editing the CaMKII6 gene to eliminate oxidation-sensitive methionine residues confers protection from ischemia/reperfusion (IR) injury. Moreover, CaMKII6 editing in mice at the time of IR enables the heart to recover function from otherwise severe damage. CaMKII6 gene editing may thus represent a permanent and advanced strategy for heart disease therapy.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 23 Mar 2024 12:44 |
| Last Modified: | 23 Mar 2024 12:44 |
| URI: | https://pred.uni-regensburg.de/id/eprint/60462 |
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