两部分的故事：快速进化的基于 CRISPR/Cas 的基因组编辑。

A Tale of Two Moieties: Rapidly Evolving CRISPR/Cas-Based Genome Editing.

机构信息

CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.

School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China.

出版信息

Trends Biochem Sci. 2020 Oct;45(10):874-888. doi: 10.1016/j.tibs.2020.06.003. Epub 2020 Jun 30.

DOI:10.1016/j.tibs.2020.06.003

PMID:32616331

Abstract

Two major moieties in genome editing are required for precise genetic changes: the locator moiety for target binding and the effector moiety for genetic engineering. By taking advantage of CRISPR/Cas, which consists of different modules for independent target binding and cleavage, a spectrum of precise and versatile genome editing technologies have been developed for broad applications in biomedical research, biotechnology, and therapeutics. Here, we briefly summarize the progress of genome editing systems from a view of both locator and effector moieties and highlight the advance of newly reported CRISPR-conjugated base editing and prime editing systems. We also underscore distinct mechanisms of off-target effects in CRISPR-conjugated systems and further discuss possible strategies to reduce off-target mutations in the future.

摘要

基因组编辑需要两个主要部分来实现精确的遗传变化

用于靶标结合的定位部分和用于基因工程的效应部分。利用 CRISPR/Cas，它由用于独立靶标结合和切割的不同模块组成，一系列精确和多功能的基因组编辑技术已经被开发出来，广泛应用于生物医学研究、生物技术和治疗学。在这里，我们简要总结了从定位部分和效应部分来看基因组编辑系统的进展，并重点介绍了新报道的 CRISPR 缀合碱基编辑和 Prime 编辑系统的进展。我们还强调了 CRISPR 缀合系统中脱靶效应的不同机制，并进一步讨论了未来降低脱靶突变的可能策略。