CRISPR-Cas9 基因编辑在人类细胞中诱导复杂的靶标效应。

CRISPR-Cas9 gene editing induced complex on-target outcomes in human cells.

机构信息

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.

出版信息

Exp Hematol. 2022 Jun;110:13-19. doi: 10.1016/j.exphem.2022.03.002. Epub 2022 Mar 15.

DOI:10.1016/j.exphem.2022.03.002

PMID:35304271

Abstract

CRISPR-Cas9 is a powerful tool for editing the genome and holds great promise for gene therapy applications. Initial concerns of gene engineering focus on off-target effects. However, in addition to short indel mutations (often <50 bp), an increasing number of studies have revealed complex on-target results after double-strand break repair by CRISPR-Cas9, such as large deletions, gene rearrangement, and loss of heterozygosity. These unintended mutations are potential safety concerns in clinical gene editing. Here, in this review, we summarize the significant findings of CRISPR-Cas9-induced on-target deleterious outcomes and discuss putative ways to achieve safe gene therapy.

摘要

CRISPR-Cas9 是编辑基因组的强大工具，在基因治疗应用中具有广阔的前景。基因工程最初的关注点是脱靶效应。然而，除了短的插入缺失突变（通常<50bp）外，越来越多的研究表明，CRISPR-Cas9 修复双链断裂后会产生复杂的靶标结果，如大片段缺失、基因重排和杂合性丢失。这些非预期的突变是临床基因编辑中的潜在安全隐患。在本文综述中，我们总结了 CRISPR-Cas9 诱导的靶标有害结果的重要发现，并讨论了实现安全基因治疗的可能方法。