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A precise and efficient adenine base editor

Mol Ther. 2022-07; 
Tianxiang Tu , Zongming Song , Xiaoyu Liu , Shengxing Wang , Xiaoxue He , Haitao Xi , Jiahua Wang , Tong Yan , Haoran Chen , Zhenwu Zhang , Xiujuan Lv , Jineng Lv , Xiu-Feng Huang , Junzhao Zhao , Chao-Po Lin , Caixia Gao , Jinwei Zhang , Feng Gu
Products/Services Used Details Operation
Gene Synthesis To generate PABE-8e and PABE-9e expression vectors, the tRNA editing deaminase ecTadA-8e, 32aa linker, and nSpCas9 (D10A)sequences were codon optimized for cereal plants and synthesized (GenScript, Nanjing, China). Get A Quote

摘要

Adenine base editors (ABEs) are novel genome-editing tools, and their activity has been greatly enhanced by eight additional mutations, thus named ABE8e. However, elevated catalytic activity was concomitant with frequent generation of bystander mutations. This bystander effect precludes its safe applications required in human gene therapy. To develop next-generation ABEs that are both catalytically efficient and positionally precise, we performed combinatorial engineering of NG-ABE8e. We identify a novel variant (NG-ABE9e), which harbors nine mutations. NG-ABE9e exhibits robust and precise base-editing activity in human cells, with more than 7-fold bystander editing reduction at some sites, compared with NG-ABE... More

关键词

ABE; bystander effect; engineering; gene therapy; genome editing.
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