《生命科学》 2022, 34(10): 1289-1304
碱基编辑器在基因治疗中的潜在安全性风险及解决方案研究进展
摘 要：
碱基编辑器 (base editor, BE) 是一种由脱氨酶与人工核酸结合蛋白结合形成的基因编辑工具，可以对单个碱基进行定点替换，以达到改变核酸序列的目的。其主要特点是能够在不产生核酸完全断裂的条件下，进行高效的碱基编辑，BE 在动植物育种以及遗传性疾病的基因治疗领域已经显示出巨大的应用价值。目前已报道的碱基编辑器包括胞嘧啶碱基编辑器、腺嘌呤碱基编辑器、糖苷酶碱基编辑器、双碱基编辑器、线粒体碱基编辑器以及RNA 编辑器等。然而，各种碱基编辑器中含有的两个主要功能元件，即脱氨酶和人工核酸结合蛋白，均有脱靶效应，为本技术的广泛应用带来严重的安全隐患。本文通过对不同碱基编辑工具的种类特点、疾病模型治疗现状以及安全性问题和解决方案进行综述，希望对后续的碱基编辑技术的优化研究提供参考。
通讯作者：邹庆剑 , Email:wyuchemzqj@126.com 赖良学 , Email:lai_liangxue@gibh.ac.cn
Abstract:
The base editor (BE) is a gene editing tool formed by fusing deaminase with artificial nucleic acid binding protein, which is able to realize specific base replacement on target sites of genome. The main feature of BEs is that base replacement could be conducted with a high efficiency without creation of DNA or RNA breaking. Therefore, it has exhibited great application in generation of new strains of animal and plants and gene therapy of human genetic diseases. A variety of BEs have been reported previously, including cytosine BE, adenine BE, glycosidase BE, dual BE, mitochondrial BE, RNA BE, and so on. However, both of the two main functional components existing in every BE, i.e. deaminase and artificial nucleic acid binding protein, are able to cause off-target effects, which gives rise to serious security risks for their applications. In this review, we have described the characteristics of each BE, their potential applications, safety concerns and corresponding solutions in gene therapy, hoping to provide useful information for further base editing optimization in the future.
Communication Author：ZOU Qing-Jian , Email:wyuchemzqj@126.com LAI Liang-Xue , Email:lai_liangxue@gibh.ac.cn
