CRISPR Modeling and Correction of Cardiovascular Disease.
CRISPR Modeling and Correction of Cardiovascular Disease.
复制标题
CRISPR建模和心血管疾病的纠正。
DOI：
10.1161/circresaha.122.320496
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发表时间：
2022-06-10
影响因子：
20.1
通讯作者：
Olson, Eric N.
中科院分区：
文献类型：
--
作者：
Liu, Ning;Olson, Eric N.
心血管疾病仍然是发达国家发病率和死亡率的主要原因。近几十年来，人们一直致力于确定患病心脏和血管系统的分子和病理生理学特征。小鼠模型在阐明复杂的信号通路、遗传和表观遗传调控回路以及心血管疾病基础上的多细胞相互作用方面特别强大。CRISPR基因组编辑的出现开创了心血管研究的新时代，并为疾病的遗传校正带来了可能性。下一代测序技术大大加快了致病突变的识别，基因编辑的进步使这些突变在小鼠和患者源性诱导多能干细胞中的快速建模成为可能。通过在体内递送基因编辑组件来纠正心血管疾病的遗传驱动因素的能力，虽然仍然面临挑战，但代表了一个令人兴奋的治疗前沿。在这篇综述中，我们概述了心血管疾病的机制以及CRISPR基因组编辑在疾病建模和校正中的潜在应用。我们还讨论了小鼠可以忠实地模拟心血管疾病的程度以及未来的机遇和挑战。
Cardiovascular disease remains the leading cause of morbidity and mortality in the developed world. In recent decades, extraordinary effort has been devoted to defining the molecular and pathophysiological characteristics of the diseased heart and vasculature. Mouse models have been especially powerful in illuminating the complex signaling pathways, genetic and epigenetic regulatory circuits and multi-cellular interactions that underlie cardiovascular disease. The advent of CRISPR genome editing has ushered in a new era of cardiovascular research and possibilities for genetic correction of disease. Next generation sequencing technologies have greatly accelerated the identification of disease-causing mutations, and advances in gene editing have enabled the rapid modeling of these mutations in mice and patient-derived induced pluripotent stem cells. The ability to correct the genetic drivers of cardiovascular disease through delivery of gene editing components in vivo, while still facing challenges, represents an exciting therapeutic frontier. In this review, we provide an overview of cardiovascular disease mechanisms and the potential applications of CRISPR genome editing for disease modeling and correction. We also discuss the extent to which mice can faithfully model cardiovascular disease and the opportunities and challenges that lie ahead.