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Peptide fusion improves prime editing efficiency

Author

Listed:
  • Minja Velimirovic

    (Brigham and Women’s Hospital and Harvard Medical School
    Centre Hospitalier Universitaire de Québec Research Center–Université Laval, Québec)

  • Larissa C. Zanetti

    (Brigham and Women’s Hospital and Harvard Medical School
    Hospital Israelita Albert Einstein)

  • Max W. Shen

    (Broad Institute of Harvard and MIT)

  • James D. Fife

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Lin Lin

    (Hubrecht Institute)

  • Minsun Cha

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Ersin Akinci

    (Brigham and Women’s Hospital and Harvard Medical School
    Akdeniz University)

  • Danielle Barnum

    (Brigham and Women’s Hospital and Harvard Medical School
    Vrije Universiteit Amsterdam, Medical School of V)

  • Tian Yu

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Richard I. Sherwood

    (Brigham and Women’s Hospital and Harvard Medical School)

Abstract

Prime editing enables search-and-replace genome editing but is limited by low editing efficiency. We present a high-throughput approach, the Peptide Self-Editing sequencing assay (PepSEq), to measure how fusion of 12,000 85-amino acid peptides influences prime editing efficiency. We show that peptide fusion can enhance prime editing, prime-enhancing peptides combine productively, and a top dual peptide-prime editor increases prime editing significantly in multiple cell lines across dozens of target sites. Top prime-enhancing peptides function by increasing translation efficiency and serve as broadly useful tools to improve prime editing efficiency.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31270-y
    DOI: 10.1038/s41467-022-31270-y
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    References listed on IDEAS

    as
    1. Max W. Shen & Mandana Arbab & Jonathan Y. Hsu & Daniel Worstell & Sannie J. Culbertson & Olga Krabbe & Christopher A. Cassa & David R. Liu & David K. Gifford & Richard I. Sherwood, 2018. "Predictable and precise template-free CRISPR editing of pathogenic variants," Nature, Nature, vol. 563(7733), pages 646-651, November.
    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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    Cited by:

    1. Jianli Tao & Daniel E. Bauer & Roberto Chiarle, 2023. "Assessing and advancing the safety of CRISPR-Cas tools: from DNA to RNA editing," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. 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.
    3. Youcai Xiong & Yinyu Su & Ruigao He & Xiaosong Han & Sheng Li & Minghuan Liu & Xiaoning Xi & Zijia Liu & Heng Wang & Shengsong Xie & Xuewen Xu & Kui Li & Jifeng Zhang & Jie Xu & Xinyun Li & Shuhong Zh, 2025. "EXPERT expands prime editing efficiency and range of large fragment edits," Nature Communications, Nature, vol. 16(1), pages 1-13, December.

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