@article{31195eb4f5be4133abc071eb64f2d2d6,
title = "Ablation of CaMKIId oxidation by CRISPR-Cas9 base editing as a therapy for cardiac disease",
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 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.",
author = "Simon Lebek and Francesco Chemello and Caravia, {Xurde M.} and Wei Tan and Hui Li and Kenian Chen and Lin Xu and Ning Liu and Rhonda Bassel-Duby and Olson, {Eric N.}",
note = "Funding Information: We thank A. Chai, Y. Zhang, and all other members of the Olson laboratory for helpful discussions; D. Alzhanov for technical assistance; J. Cabrera for graphics; J. Xu and Y. J. Kim from the CRI for Illumina NextSeq sequencing; C. Rodriguez-Caycedo for help with the iPSCs; J. Wansapura from the UTSW Advanced Imaging Research Center for mouse MRIs; Y. Zhang and the Boston Children's Hospital Viral Core for virus production; J. Shelton from the Molecular Histopathology Core for helping with histology; the UTSW McDermott Center Sanger Sequencing Core; the UTSW McDermott Center Next Generation Sequencing Core; and the UTSW Flow Cytometry Core. Funding was provided by the following: National Institutes of Health grant R01HL130253 (to E.N.O. and R.B.-D.); National Institutes of Health grant R01HL157281 (to E.N.O. and R.B.-D.); National Institutes of Health grant P50HD087351 (to E.N.O. and R.B.-D.); Fondation Leducq Transatlantic Network of Excellence (to E.N.O.); Robert A. Welch Foundation 1-0025 (to E.N.O.); German Research Foundation (DFG) LE 5009/1-1 (to S.L.); German Cardiac Society (to S.L.); Cancer Prevention and Research Institute of Texas RP210099 Publisher Copyright: {\textcopyright} 2023 American Association for the Advancement of Science. All rights reserved.",
year = "2023",
month = jan,
day = "13",
doi = "10.1126/science.ade1105",
language = "English (US)",
volume = "379",
pages = "179--185",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6628",
}