Reducing off-target effects of DdCBEs by reversing amino acid charge near DNA interaction sites  

作　　者：Long Xie Yaqi Cao Di Li Mengxue Ma Danrong Jiao Hu Feng Zhenrui Zuo Erwei Zuo 

机构地区：[1]Shenzhen Branch,Guangdong Laboratory for Lingnan Modern Agriculture,Key Laboratory of Synthetic Biology,Ministry of Agriculture and Rural Affairs,Agricultural Genomics Institute at Shenzhen,Chinese Academy of Agricultural Sciences,Shenzhen,Guangdong,China

出　　处：《Cell Research》2024年第12期877-881,共5页细胞研究（英文版）

摘　　要：Dear Editor,DddA_(tox)-derived cytosine base editors(DdCBEs)can mediate precise,CRISPR-independent editing of mitochondrial DNA(mtDNA),but were recently shown to potentially introduce extensive and non-trivial off-target effects throughout the genome,1,2 presenting a significant obstacle for research applications and an obvious safety issue for use in clinical therapies of hereditary mitochondrial disorders.Here,utilizing the crystal structure of DddAtox in complex with DNA,we predicted DNA-binding sites on the DddAtox protein surface and generated variants by converting positively charged residues at these sites to negatively charged amino acids.

关 键 词：TRIVIAL utilizing PRECISE 

分 类 号：Q25[生物学—细胞生物学]