Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
Università di Pavia, Istituti Clinici Scientifici Maugeri, Pavia, Italy.
Adv Exp Med Biol. 2023;1396:115-127. doi: 10.1007/978-981-19-5642-3_8.
Inherited arrhythmic disorders are a group of heterogeneous diseases predisposing to life-threatening arrhythmias and sudden cardiac death. Their diagnosis is not always simple due to incomplete penetrance and genetic heterogeneity. Furthermore, the available treatments are usually invasive and merely preventive. Genome editing and especially CRISPR/Cas9 technologies have the potential to correct the genetic arrhythmogenic substrate, thereby offering a cure for these fatal diseases. To date, genome editing has allowed reproducing cardiac arrhythmias in vitro, providing a robust platform for variant pathogenicity, mechanistic, and drug-testing studies. However, in vivo approaches still need profound research regarding safety, specificity, and efficiency of the methods.
遗传性心律失常疾病是一组异质性疾病，易导致危及生命的心律失常和心源性猝死。由于不完全外显和遗传异质性，其诊断并不总是简单的。此外，现有的治疗方法通常是有创的，只能起到预防作用。基因组编辑，特别是 CRISPR/Cas9 技术，有可能纠正心律失常的遗传基础，从而为这些致命疾病提供治愈方法。迄今为止，基因组编辑已经允许在体外重现心律失常，为变异致病性、机制和药物测试研究提供了一个强大的平台。然而，体内方法在安全性、方法的特异性和效率方面仍需要深入研究。
