基因组编辑
基因组
计算生物学
生物
遗传学
基因
细胞生物学
作者
Chunyan Ren,Yanshan Liu,Yu-Shan He,Linpei Zhang,Junhua Rao,Yijian Rao,Jian‐Huan Chen
出处
期刊:Cell Reports
[Elsevier]
日期:2024-03-01
卷期号:43 (3): 113878-113878
标识
DOI:10.1016/j.celrep.2024.113878
摘要
Summary
Cytidine deaminase defines the properties of cytosine base editors (CBEs) for C-to-T conversion. Replacing the cytidine deaminase rat APOBEC1 (rA1) in CBEs with a human APOBEC3A (hA3A) improves CBE properties. However, the potential CBE application of macaque A3A orthologs remains undetermined. Our current study develops and evaluates engineered CBEs based on Macaca fascicularis A3A (mA3A). Here, we demonstrate that BE4-mA3A and its RNA-editing-derived variants exhibit improved CBE properties, except for DNA off-target activity, compared to BE3-rA1 and BE4-rA1. Unexpectedly, deleting Ser-Val-Arg (SVR) in BE4-mA3A dramatically reduces DNA and RNA off-target activities and improves editing accuracy, with on-target efficiency unaffected. In contrast, a chimeric BE4-hA3A-SVR+ shows editing efficiency increased by about 50%, with other properties unaffected. Our findings demonstrate that mA3A-based CBEs could provide prototype options with advantages over rA1- and hA3A-based CBEs for further optimization, highlighting the importance of the SVR motif in defining CBE intrinsic properties.
科研通智能强力驱动
Strongly Powered by AbleSci AI