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ABE-ultramax for high-efficiency biallelic adenine base editing in zebrafish

Author

Listed:
  • Wei Qin

    (Oklahoma Medical Research Foundation)

  • Fang Liang

    (South China Normal University)

  • Sheng-Jia Lin

    (Oklahoma Medical Research Foundation)

  • Cassidy Petree

    (Oklahoma Medical Research Foundation)

  • Kevin Huang

    (Oklahoma Medical Research Foundation)

  • Yu Zhang

    (Oklahoma Medical Research Foundation)

  • Lin Li

    (South China Normal University
    South China Normal University)

  • Pratishtha Varshney

    (Oklahoma Medical Research Foundation)

  • Philippe Mourrain

    (Stanford University)

  • Yanmei Liu

    (South China Normal University
    South China Normal University)

  • Gaurav K. Varshney

    (Oklahoma Medical Research Foundation)

Abstract

Advancements in CRISPR technology, particularly the development of base editors, revolutionize genetic variant research. When combined with model organisms like zebrafish, base editors significantly accelerate and refine in vivo analysis of genetic variations. However, base editors are restricted by protospacer adjacent motif (PAM) sequences and specific editing windows, hindering their applicability to a broad spectrum of genetic variants. Additionally, base editors can introduce unintended mutations and often exhibit reduced efficiency in living organisms compared to cultured cell lines. Here, we engineer a suite of adenine base editors (ABEs) called ABE-Ultramax (Umax), demonstrating high editing efficiency and low rates of insertions and deletions (indels) in zebrafish. The ABE-Umax suite of editors includes ABEs with shifted, narrowed, or broadened editing windows, reduced bystander mutation frequency, and highly flexible PAM sequence requirements. These advancements have the potential to address previous challenges in disease modeling and advance gene therapy applications.

Suggested Citation

  • Wei Qin & Fang Liang & Sheng-Jia Lin & Cassidy Petree & Kevin Huang & Yu Zhang & Lin Li & Pratishtha Varshney & Philippe Mourrain & Yanmei Liu & Gaurav K. Varshney, 2024. "ABE-ultramax for high-efficiency biallelic adenine base editing in zebrafish," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49943-1
    DOI: 10.1038/s41467-024-49943-1
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