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High performance TadA-8e derived cytosine and dual base editors with undetectable off-target effects in plants

Author

Listed:
  • Tingting Fan

    (University of Electronic Science and Technology of China
    Southwest University)

  • Yanhao Cheng

    (University of Maryland)

  • Yuechao Wu

    (Yangzhou University
    Yangzhou University)

  • Shishi Liu

    (University of Electronic Science and Technology of China)

  • Xu Tang

    (Southwest University)

  • Yao He

    (University of Electronic Science and Technology of China)

  • Shanyue Liao

    (University of Electronic Science and Technology of China)

  • Xuelian Zheng

    (Southwest University)

  • Tao Zhang

    (Yangzhou University
    Yangzhou University)

  • Yiping Qi

    (University of Maryland
    University of Maryland)

  • Yong Zhang

    (Southwest University)

Abstract

Cytosine base editors (CBEs) and adenine base editors (ABEs) enable precise C-to-T and A-to-G edits. Recently, ABE8e, derived from TadA-8e, enhances A-to-G edits in mammalian cells and plants. Interestingly, TadA-8e can also be evolved to confer C-to-T editing. This study compares engineered CBEs derived from TadA-8e in rice and tomato cells, identifying TadCBEa, TadCBEd, and TadCBEd_V106W as efficient CBEs with high purity and a narrow editing window. A dual base editor, TadDE, promotes simultaneous C-to-T and A-to-G editing. Multiplexed base editing with TadCBEa and TadDE is demonstrated in transgenic rice, with no off-target effects detected by whole genome and transcriptome sequencing, indicating high specificity. Finally, two crop engineering applications using TadDE are shown: introducing herbicide resistance alleles in OsALS and creating synonymous mutations in OsSPL14 to resist OsMIR156-mediated degradation. Together, this study presents TadA-8e derived CBEs and a dual base editor as valuable additions to the plant editing toolbox.

Suggested Citation

  • Tingting Fan & Yanhao Cheng & Yuechao Wu & Shishi Liu & Xu Tang & Yao He & Shanyue Liao & Xuelian Zheng & Tao Zhang & Yiping Qi & Yong Zhang, 2024. "High performance TadA-8e derived cytosine and dual base editors with undetectable off-target effects in plants," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49473-w
    DOI: 10.1038/s41467-024-49473-w
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    References listed on IDEAS

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    1. 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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