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Engineered minimal type I CRISPR-Cas system for transcriptional activation and base editing in human cells

Author

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  • Jing Guo

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

  • Luyao Gong

    (Chinese Academy of Sciences)

  • Haiying Yu

    (Chinese Academy of Sciences)

  • Ming Li

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

  • Qiaohui An

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

  • Zhenquan Liu

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

  • Shuru Fan

    (Chinese Academy of Sciences)

  • Changjialian Yang

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

  • Dahe Zhao

    (Chinese Academy of Sciences)

  • Jing Han

    (Chinese Academy of Sciences)

  • Hua Xiang

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

Abstract

Type I CRISPR-Cas systems are widespread and have exhibited high versatility and efficiency in genome editing and gene regulation in prokaryotes. However, due to the multi-subunit composition and large size, their application in eukaryotes has not been thoroughly investigated. Here, we demonstrate that the type I-F2 Cascade, the most compact among type I systems, with a total gene size smaller than that of SpCas9, can be developed for transcriptional activation in human cells. The efficiency of the engineered I-F2 tool can match or surpass that of dCas9. Additionally, we create a base editor using the I-F2 Cascade, which induces a considerably wide editing window (~30 nt) with a bimodal distribution. It can expand targetable sites, which is useful for disrupting functional sequences and genetic screening. This research underscores the application of compact type I systems in eukaryotes, particularly in the development of a base editor with a wide editing window.

Suggested Citation

  • Jing Guo & Luyao Gong & Haiying Yu & Ming Li & Qiaohui An & Zhenquan Liu & Shuru Fan & Changjialian Yang & Dahe Zhao & Jing Han & Hua Xiang, 2024. "Engineered minimal type I CRISPR-Cas system for transcriptional activation and base editing in human cells," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51695-x
    DOI: 10.1038/s41467-024-51695-x
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