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Enhancement of a prime editing system via optimal recruitment of the pioneer transcription factor P65

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  • Ronghao Chen

    (Nankai University
    Chinese Academy of Sciences
    National Technology Innovation Center of Synthetic Biology)

  • Yu Cao

    (Nankai University
    Chinese Academy of Sciences
    National Technology Innovation Center of Synthetic Biology)

  • Yajing Liu

    (Nankai University
    Chinese Academy of Sciences
    National Technology Innovation Center of Synthetic Biology)

  • Dongdong Zhao

    (Chinese Academy of Sciences
    National Technology Innovation Center of Synthetic Biology)

  • Ju Li

    (Tianjin Normal University)

  • Zhihui Cheng

    (Nankai University)

  • Changhao Bi

    (Chinese Academy of Sciences
    National Technology Innovation Center of Synthetic Biology)

  • Xueli Zhang

    (Chinese Academy of Sciences
    National Technology Innovation Center of Synthetic Biology)

Abstract

Prime editing is a versatile gene editing tool that enables precise sequence changes of all types in the genome, but its application is rather limited by the editing efficiency. Here, we first apply the Suntag system to recruit the transcription factor P65 and enhance the desired editing outcomes in the prime editing system. Next, MS2 hairpins are used to recruit MS2-fused P65 and confirmed that the recruitment of the P65 protein could effectively improve the prime editing efficiency in both the PE3 and PE5 systems. Moreover, this suggests the increased editing efficiency is most likely associated with the induction of chromatin accessibility change by P65. In conclusion, we apply different systems to recruit P65 and enhance the prime editing efficiency of various PE systems. Furthermore, our work provides a variety of methods to work as protein scaffolds for screening target factors and thus supports further optimization of prime editing systems.

Suggested Citation

  • Ronghao Chen & Yu Cao & Yajing Liu & Dongdong Zhao & Ju Li & Zhihui Cheng & Changhao Bi & Xueli Zhang, 2023. "Enhancement of a prime editing system via optimal recruitment of the pioneer transcription factor P65," Nature Communications, Nature, vol. 14(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-35919-0
    DOI: 10.1038/s41467-023-35919-0
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    References listed on IDEAS

    as
    1. Myungjae Song & Jung Min Lim & Seonwoo Min & Jeong-Seok Oh & Dong Young Kim & Jae-Sung Woo & Hiroshi Nishimasu & Sung-Rae Cho & Sungroh Yoon & Hyongbum Henry Kim, 2021. "Generation of a more efficient prime editor 2 by addition of the Rad51 DNA-binding domain," Nature Communications, Nature, vol. 12(1), pages 1-8, December.
    2. 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.
    3. Minja Velimirovic & Larissa C. Zanetti & Max W. Shen & James D. Fife & Lin Lin & Minsun Cha & Ersin Akinci & Danielle Barnum & Tian Yu & Richard I. Sherwood, 2022. "Peptide fusion improves prime editing efficiency," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
    4. Guiquan Zhang & Yao Liu & Shisheng Huang & Shiyuan Qu & Daolin Cheng & Yuan Yao & Quanjiang Ji & Xiaolong Wang & Xingxu Huang & Jianghuai Liu, 2022. "Enhancement of prime editing via xrRNA motif-joined pegRNA," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    5. 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.
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