Shan Qi-wei, Gao Cai-xia
State Key Laboratory of Plant Cell and Chromosome Engineering, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
Yi Chuan. 2015 Oct;37(10):953-73. doi: 10.16288/j.yczz.15-156.
Genome editing technologies using engineered nucleases have been widely used in many model organisms. Genome editing with sequence-specific nuclease (SSN) creates DNA double-strand breaks (DSBs) in the genomic target sites that are primarily repaired by the non-homologous end joining (NHEJ) or homologous recombination (HR) pathways, which can be employed to achieve targeted genome modifications such as gene mutations, insertions, replacements or chromosome rearrangements. There are three major SSNs─zinc finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN) and clustered regularly interspaced short palindromic repeats/CRISPR-associated 9 (CRISPR/Cas9) system. In contrast to ZFN and TALEN, which require substantial protein engineering to each DNA target, the CRISPR/Cas9 system requires only a change in the guide RNA. For this reason, the CRISPR/Cas9 system is a simple, inexpensive and versatile tool for genome engineering. Furthermore, a modified version of the CRISPR/Cas9 system has been developed to recruit heterologous domains that can regulate endogenous gene expression, such as activation, depression and epigenetic regulation. In this review, we summarize the development and applications of genome editing technologies for basic research and biotechnology, as well as highlight challenges and future directions, with particular emphasis on plants.
使用工程核酸酶的基因组编辑技术已在许多模式生物中广泛应用。用序列特异性核酸酶(SSN)进行基因组编辑会在基因组靶位点产生DNA双链断裂(DSB),这些断裂主要通过非同源末端连接(NHEJ)或同源重组(HR)途径进行修复,可用于实现靶向基因组修饰,如基因突变、插入、替换或染色体重排。有三种主要的SSN——锌指核酸酶(ZFN)、转录激活样效应物核酸酶(TALEN)和成簇规律间隔短回文重复序列/CRISPR相关蛋白9(CRISPR/Cas9)系统。与需要对每个DNA靶点进行大量蛋白质工程改造的ZFN和TALEN不同,CRISPR/Cas9系统只需要改变引导RNA。因此,CRISPR/Cas9系统是一种用于基因组工程的简单、廉价且通用的工具。此外,已开发出CRISPR/Cas9系统的一种改良版本,用于招募可调节内源性基因表达的异源结构域,如激活、抑制和表观遗传调控。在本综述中,我们总结了基因组编辑技术在基础研究和生物技术方面的发展与应用,并强调了挑战和未来方向,尤其侧重于植物。