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Phage peptides mediate precision base editing with focused targeting window.

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 G8P_PD, could improve the specificity of Cas9 nuclease. Herein, we investigate the applicability of G8P_PD as molecular modulators of BEs. We show that G8P_PD can improve cytidine base editor (CBEs) and adenine base editor (ABE) to more focused targeting windows. Notably, in a cell-based disease model, G8P_PD increases the percentage of perfectly edited gene alleles by BEs from less than 4% to more than 38% of the whole population. In addition, G8P_PD 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.

SUBMITTER: Jia K

PROVIDER: S-EPMC8964698 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Phage peptides mediate precision base editing with focused targeting window.

Jia Kun K Cui Yan-Ru YR Huang Shisheng S Yu Peihong P Lian Zhengxing Z Ma Peixiang P Liu Jia J

Nature communications 20220329 1

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 G8PP ...[more]

PMID: 35351888

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