研究人员描述了一种可能适用于广泛心脏病患者的心脏保护策略。研究人员使用碱基编辑来去除了CaMKIIδ的氧化激活位点，这是心脏疾病的一个主要驱动因素。研究人员在来自人类诱导多能干细胞的心肌细胞中显示，编辑CaMKIIδ基因来消除对氧化敏感的蛋氨酸残基可保护其免受缺血/再灌注（IR）损伤。此外，在IR发生时对小鼠进行CaMKIIδ基因编辑，可使心脏从其他严重损伤中恢复功能。因此，CaMKIIδ基因编辑可能代表了一种永久性的、先进的心脏疾病治疗策略。
据了解，CRISPR-Cas9基因编辑正在成为基因组突变的一种前瞻性疗法。然而，目前的编辑方法主要是针对具有特定突变的相对较小的患者群。
附：英文原文
Title: Ablation of CaMKIIδ oxidation by CRISPR-Cas9 base editing as a therapy for cardiac disease
Author: Simon Lebek, Francesco Chemello, Xurde M. Caravia, Wei Tan, Hui Li, Kenian Chen, Lin Xu, Ning Liu, Rhonda Bassel-Duby, Eric N. Olson
Issue&Volume: 2023-01-13
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 CaMKIIδ gene to eliminate oxidation-sensitive methionine residues confers protection from ischemia/reperfusion (IR) injury. Moreover, CaMKIIδ editing in mice at the time of IR enables the heart to recover function from otherwise severe damage. CaMKIIδ gene editing may thus represent a permanent and advanced strategy for heart disease therapy.
DOI: ade1105
Source: https://www.science.org/doi/10.1126/science.ade1105