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Enhanced C-To-T and A-To-G Base Editing in Mitochondrial DNA with Engineered DdCBE and TALED

Adv Sci (Weinh). 2023-11; 
Yinghui Wei, Ming Jin, Shuhong Huang, Fangyao Yao, Ningxin Ren, Kun Xu, Shangpu Li, Pengfei Gao, Yingsi Zhou, Yulin Chen, Hui Yang, Wen Li, Chunlong Xu, Meiling Zhang, Xiaolong Wang
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Codon Optimization … Codon-optimized sequences for human cell expression were obtained from GenScript. The TALE binding sequences, targeting sequences, and amino acid sequences of all DdCBEs, … Get A Quote

摘要

Mitochondrial base editing with DddA-derived cytosine base editor (DdCBE) is limited in the accessible target sequences and modest activity. Here, the optimized DdCBE tools is presented with improved editing activity and expanded C-to-T targeting scope by fusing DddA11 variant with different cytosine deaminases with single-strand DNA activity. Compared to previous DdCBE based on DddA11 variant alone, fusion of the activation-induced cytidine deaminase (AID) from Xenopus laevis not only permits cytosine editing of 5'-GC-3' sequence, but also elevates editing efficiency at 5'-TC-3', 5'-CC-3', and 5'-GC-3' targets by up to 25-, 10-, and 6-fold, respectively. Furthermore, the A-to-G editing efficiency is significan... More

關鍵詞

DdCBE, TALED, disease modeling, mitochondrial base editing
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