Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA.
Department of Bioengineering, Stanford University, Stanford, CA, USA.
Nat Rev Cardiol. 2022 Aug;19(8):505-521. doi: 10.1038/s41569-021-00669-3. Epub 2022 Feb 10.
Many novel CRISPR-based genome-editing tools, with a wide variety of applications, have been developed in the past few years. The original CRISPR-Cas9 system was developed as a tool to alter genomic sequences in living organisms in a simple way. However, the functions of new CRISPR tools are not limited to conventional genome editing mediated by non-homologous end-joining or homology-directed repair but expand into gene-expression control, epigenome editing, single-nucleotide editing, RNA editing and live-cell imaging. Furthermore, genetic perturbation screening by multiplexing guide RNAs is gaining popularity as a method to identify causative genes and pathways in an unbiased manner. New CRISPR tools can also be applied to ex vivo or in vivo therapeutic genome editing for the treatment of conditions such as hyperlipidaemia. In this Review, we first provide an overview of the diverse new CRISPR tools that have been developed to date. Second, we summarize how these new CRISPR tools are being used to study biological processes and disease mechanisms in cardiovascular research and medicine. Finally, we discuss the prospect of therapeutic genome editing by CRISPR tools to cure genetic cardiovascular diseases.
在过去的几年中，已经开发出了许多新型基于 CRISPR 的基因组编辑工具，具有广泛的应用。最初的 CRISPR-Cas9 系统被开发为一种简单的方法来改变生物体内的基因组序列。然而，新的 CRISPR 工具的功能不仅限于非同源末端连接或同源定向修复介导的常规基因组编辑，而是扩展到基因表达控制、表观基因组编辑、单核苷酸编辑、RNA 编辑和活细胞成像。此外，通过多路向导 RNA 进行遗传扰动筛选作为一种以非偏倚方式识别因果基因和途径的方法越来越受欢迎。新的 CRISPR 工具也可应用于治疗性基因组编辑，用于治疗高脂血症等疾病。在这篇综述中，我们首先概述了迄今为止开发的各种新型 CRISPR 工具。其次，我们总结了这些新的 CRISPR 工具如何用于研究心血管研究和医学中的生物学过程和疾病机制。最后，我们讨论了 CRISPR 工具治疗性基因组编辑治愈遗传性心血管疾病的前景。
