Phage peptides mediate precision base editing with focused targeting window

Kun Jia, Yan-ru Cui, Shisheng Huang, Peihong Yu, Zhengxing Lian, Peixiang Ma and Jia Liu ()
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Kun Jia: ShanghaiTech University
Yan-ru Cui: ShanghaiTech University
Shisheng Huang: ShanghaiTech University
Peihong Yu: ShanghaiTech University
Zhengxing Lian: China Agricultural University
Peixiang Ma: ShanghaiTech University
Jia Liu: ShanghaiTech University

Nature Communications, 2022, vol. 13, issue 1, 1-10

Abstract: Abstract Base editors (BEs) are genome engineering tools that can generate nucleotide substitutions without introducing double-stranded breaks (DSBs). A variety of strategies have been developed to improve the targeting scope and window of BEs. In a previous study, we found that a bacteriophage-derived peptide, referred to as G8PPD, could improve the specificity of Cas9 nuclease. Herein, we investigate the applicability of G8PPD as molecular modulators of BEs. We show that G8PPD can improve cytidine base editor (CBEs) and adenine base editor (ABE) to more focused targeting windows. Notably, in a cell-based disease model, G8PPD increases the percentage of perfectly edited gene alleles by BEs from less than 4% to more than 38% of the whole population. In addition, G8PPD can improve the targeting scope of BE in mouse embryos. In summary, our study presents the peptidyl modulators that can improve BEs for precision base editing.

Date: 2022
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DOI: 10.1038/s41467-022-29365-7

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