基因编辑与基因毒性：靶向脱靶效应
Gene Editing and Genotoxicity: Targeting the Off-Targets.
作者信息
Blattner Georges, Cavazza Alessia, Thrasher Adrian J, Turchiano Giandomenico
机构信息
Infection, Immunity and Inflammation Research and Teaching Department, Zayed Centre for Research into Rare Disease in Children, Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.
出版信息
Front Genome Ed. 2020 Dec 10;2:613252. doi: 10.3389/fgeed.2020.613252. eCollection 2020.
Abstract
Gene editing technologies show great promise for application to human disease as a result of rapid developments in targeting tools notably based on ZFN, TALEN, and CRISPR-Cas systems. Precise modification of a DNA sequence is now possible in mature human somatic cells including stem and progenitor cells with increasing degrees of efficiency. At the same time new technologies are required to evaluate their safety and genotoxicity before widespread clinical application can be confidently implemented. A number of methodologies have now been developed in an attempt to predict expected and unexpected modifications occurring during gene editing. This review surveys the techniques currently available as state of the art, highlighting benefits and limitations, and discusses approaches that may achieve sufficient accuracy and predictability for application in clinical settings.
摘要
由于靶向工具特别是基于锌指核酸酶（ZFN）、转录激活因子样效应物核酸酶（TALEN）和规律成簇间隔短回文重复序列及其相关蛋白系统（CRISPR-Cas）系统的快速发展，基因编辑技术在人类疾病应用方面显示出巨大的前景。现在，在包括干细胞和祖细胞在内的成熟人类体细胞中，以越来越高的效率对DNA序列进行精确修饰已成为可能。与此同时，在能够自信地广泛应用于临床之前，需要新技术来评估其安全性和基因毒性。目前已经开发了许多方法，试图预测基因编辑过程中发生的预期和意外修饰。本综述调查了当前作为最先进技术可用的技术，突出了其优点和局限性，并讨论了在临床环境中应用时可能实现足够准确性和可预测性的方法。
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