单碱基编辑技术的应用研究进展

doi:10.16431/j.cnki.1671-7236.2021.12.008

摘要/Abstract

摘要： 单碱基编辑(base editor,BE)技术是一种基于CRISPR/Cas9技术发展而来的新一代基因编辑技术。与传统的基因编辑技术相比,单碱基编辑具有高效、安全、副产物少等优势,其正逐渐取代传统的锌指蛋白核酸酶(zinc finger nuclease,ZFN)技术、转录激活样效应因子核酸酶(transcription activator-like effector nuclease,TALEN)技术、成簇的规律间隔短回文重复序列及相关蛋白Cas(clustered regularly interspaced short palindromic repeats/Cas,CRISPR/Cas)技术,成为主流的基因编辑技术。单碱基编辑技术极大地促进了家畜基因编辑育种、人类遗传疾病基因治疗等领域的发展。随着脱氨酶和Cas核酸酶的不断优化,单碱基编辑的准确率不断提高,靶向范围不断扩大,使该技术在生命科学领域获得更广泛的应用。作者比较了历代基因编辑技术的优点与缺点,回顾了单碱基编辑技术的主要功能结构、编辑原理和优化历程,分析了单碱基编辑技术的优势与不足,重点阐述了单碱基编辑技术在家畜抗病力、产肉率、产毛量和繁殖力等重要经济性状的改良及人类基因疾病治疗等方面的应用,并对单碱基编辑技术在单次改良家畜多个经济性状、攻克猪配子冷冻保存难题等方面的深入应用提出了设想。

关键词: 单碱基编辑; CRISPR/Cas9; 家畜育种; 疾病治疗

Abstract: Single base editor (BE) is a new generation of gene editing technology based on CRISPR/Cas9.Compared with the traditional gene editing technology, single base editing has the unique advantages of high efficiency, safety and less by-products.It is gradually replacing the traditional techniques such as zinc finger nuclease (ZFN) technology, transcription activator-like effector nuclease (TALEN) technology, clustered regularly interspaced short palindromic repeats/Cas (CRISPR/Cas) and become the mainstream gene editing technology.Single base editing technology has greatly promoted the development of livestock gene editing and human disease treatment and other research fields.With the continuous optimization of deaminase and Cas nuclease, the accuracy of single base editing is improving and the targeting range is expanding, so that the technology can be more widely used in the field of life science.The advantages and disadvantages of previous gene editing technology were compared.The main function structure, editing principle and optimization process of single base editing technology were reviewed.The advantages and disadvantages of single base editing technology were analyzed.This review focuses on the application of single base editing technology in the improvement of important economic traits such as disease resistance, meat yield, wool yield and fecundity of livestock and the treatment of human gene diseases.In this review, the further application of single base editing technology in improving multiple economic traits of livestock and overcoming the problem of pig gamete cryopreservation was proposed.

Key words: single base editing; CRISPR/Cas9; livestock breeding; disease treatment

中图分类号:

徐茜, 杨莎, 郝海生, 杜卫华, 庞云渭, 赵善江, 邹惠影, 朱化彬, 李树静, 余文莉, 赵学明. 单碱基编辑技术的应用研究进展[J]. 中国畜牧兽医, 2021, 48(12): 4403-4411.

XU Xi, YANG Sha, HAO Haisheng, DU Weihua, PANG Yunwei, ZHAO Shanjiang, ZOU Huiying, ZHU Huabin, LI Shujing, YU Wenli, ZHAO Xueming. Research Progress on Application of Single Base Editing Technology[J]. China Animal Husbandry and Veterinary Medicine, 2021, 48(12): 4403-4411.

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