Ablation of CaMKIIδ oxidation by CRISPR-Cas9 base editing as a therapy for cardiac disease.
Ablation of CaMKIIδ oxidation by CRISPR-Cas9 base editing as a therapy for cardiac disease.
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DOI：
10.1126/science.ade1105
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发表时间：
2023-01-13
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影响因子：
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CRISPR-Cas9基因编辑正在成为基因组突变的前瞻性疗法。然而，目前的编辑方法主要针对具有特定突变的相对较小的患者队列。在这里，我们描述了一种可能适用于广泛的心脏病患者的心脏保护策略。我们使用碱基编辑来消除CaMKIIδ的氧化活化位点，这是心脏病的主要驱动因素。我们在来自人类诱导多能干细胞的心肌细胞中显示，编辑CaMKIIδ基因以消除氧化敏感性甲硫氨酸残基可保护心肌免受缺血/再灌注（IR）损伤。此外，在IR时小鼠中的CaMKIIδ编辑使心脏能够从其他严重损伤中恢复功能。因此，CaMKIIδ基因编辑可能代表了心脏病治疗的永久和先进策略。
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.
CRISPR建模和心血管疾病的纠正。
影响因子：
20.1
作者：
Liu, Ning;Olson, Eric N.
通讯作者：
Olson, Eric N.
影响因子：
13.6
作者：
Chemello F;Chai AC;Li H;Rodriguez-Caycedo C;Sanchez-Ortiz E;Atmanli A;Mireault AA;Liu N;Bassel-Duby R;Olson EN
通讯作者：
Olson EN