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Improving adenine and dual base editors through introduction of TadA-8e and Rad51DBD

Nat Commun. 2023-03; 
Niannian Xue, Xu Liu, Dan Zhang, Youming Wu, Yi Zhong, Jinxin Wang, Wenjing Fan, Haixia Jiang, Biyun Zhu, Xiyu Ge, Rachel V L Gonzalez, Liang Chen, Shun Zhang, Peilu She, Zhilin Zhong, Jianjian Sun, Xi Chen, Liren Wang, Zhimin Gu, Ping Zhu, Mingyao Liu, Dali Li, Tao P Zhong, Xiaohui Zhang
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Proteins, Expression, Isolation and Analysis … sgRNAs with the modification of phosphorothioation and methoxy group were synthesized by GenScript. (Nanjing, China) (Supplementary Table 4). mRNA preparation was performed … Get A Quote

摘要

Base editors, including dual base editors, are innovative techniques for efficient base conversions in genomic DNA. However, the low efficiency of A-to-G base conversion at positions proximal to the protospacer adjacent motif (PAM) and the A/C simultaneous conversion of the dual base editor hinder their broad applications. In this study, through fusion of ABE8e with Rad51 DNA-binding domain, we generate a hyperactive ABE (hyABE) which offers improved A-to-G editing efficiency at the region (A-A) proximal to the PAM, with 1.2- to 7-fold improvement compared to ABE8e. Similarly, we develop optimized dual base editors (eA&C-BEmax and hyA&C-BEmax) with markedly improved simultaneous A/C conversion efficiency (1.2-f... More

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