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Circular RNA-mediated inverse prime editing in human cells

Author

Listed:
  • Ronghong Liang

    (Chinese Academy of Sciences)

  • Shan Wang

    (Chinese Academy of Sciences)

  • Yibo Cai

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Zhenyu Li

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Ka Ming Li

    (University of Chinese Academy of Sciences)

  • Jingjing Wei

    (Chinese Academy of Sciences)

  • Chao Sun

    (Chinese Academy of Sciences)

  • Haocheng Zhu

    (Chinese Academy of Sciences)

  • Kunling Chen

    (Chinese Academy of Sciences)

  • Caixia Gao

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

Abstract

Prime editors are restricted to performing precise edits downstream of cleavage sites, thereby limiting their editing scope. Therefore, we develop inverse prime editors (iPEs) that act upstream of the nickase cleavage site by replacing nCas9-H840A with nCas9-D10A, but the editing efficiencies are limited. To address this limitation, we develop circular RNA-mediated iPEs (ciPEs), achieving editing efficiencies ranging from 0.1% to 24.7%. Further optimization using Rep-X helicase increases editing efficiencies to a range of 2.7%–55.4%. The Rep-X-assisted ciPE system thus expands the scope of editing and improves efficiencies at genomic sites that are previously difficult to target. The Rep-X-assisted ciPE system will complement canonical PE system in enabling more extensive and efficient editing across a wider range of the human genome.

Suggested Citation

  • Ronghong Liang & Shan Wang & Yibo Cai & Zhenyu Li & Ka Ming Li & Jingjing Wei & Chao Sun & Haocheng Zhu & Kunling Chen & Caixia Gao, 2025. "Circular RNA-mediated inverse prime editing in human cells," Nature Communications, Nature, vol. 16(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59120-7
    DOI: 10.1038/s41467-025-59120-7
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