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Phage peptides mediate precision base editing with focused targeting window

Author

Listed:
  • Kun Jia

    (ShanghaiTech University
    First Affiliated Hospital of Guangzhou Medical University
    Shanghai Clinical Research and Trial Center)

  • Yan-ru Cui

    (ShanghaiTech University
    University of Chinese Academy of Sciences)

  • Shisheng Huang

    (ShanghaiTech University
    University of Chinese Academy of Sciences)

  • Peihong Yu

    (ShanghaiTech University
    University of Chinese Academy of Sciences)

  • Zhengxing Lian

    (China Agricultural University)

  • Peixiang Ma

    (ShanghaiTech University)

  • Jia Liu

    (ShanghaiTech University
    First Affiliated Hospital of Guangzhou Medical University
    Shanghai Clinical Research and Trial Center
    ShanghaiTech University)

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.

Suggested Citation

  • Kun Jia & Yan-ru Cui & Shisheng Huang & Peihong Yu & Zhengxing Lian & Peixiang Ma & Jia Liu, 2022. "Phage peptides mediate precision base editing with focused targeting window," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29365-7
    DOI: 10.1038/s41467-022-29365-7
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    References listed on IDEAS

    as
    1. Joe Bondy-Denomy & April Pawluk & Karen L. Maxwell & Alan R. Davidson, 2013. "Bacteriophage genes that inactivate the CRISPR/Cas bacterial immune system," Nature, Nature, vol. 493(7432), pages 429-432, January.
    2. Andrew V. Anzalone & Peyton B. Randolph & Jessie R. Davis & Alexander A. Sousa & Luke W. Koblan & Jonathan M. Levy & Peter J. Chen & Christopher Wilson & Gregory A. Newby & Aditya Raguram & David R. L, 2019. "Search-and-replace genome editing without double-strand breaks or donor DNA," Nature, Nature, vol. 576(7785), pages 149-157, December.
    3. Alexis C. Komor & Yongjoo B. Kim & Michael S. Packer & John A. Zuris & David R. Liu, 2016. "Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage," Nature, Nature, vol. 533(7603), pages 420-424, May.
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