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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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    References listed on IDEAS

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    1. Gregory A. Newby & Jonathan S. Yen & Kaitly J. Woodard & Thiyagaraj Mayuranathan & Cicera R. Lazzarotto & Yichao Li & Heather Sheppard-Tillman & Shaina N. Porter & Yu Yao & Kalin Mayberry & Kelcee A. , 2021. "Base editing of haematopoietic stem cells rescues sickle cell disease in mice," Nature, Nature, vol. 595(7866), pages 295-302, July.
    2. Marion Rosello & Malo Serafini & Luca Mignani & Dario Finazzi & Carine Giovannangeli & Marina C. Mione & Jean-Paul Concordet & Filippo Del Bene, 2022. "Disease modeling by efficient genome editing using a near PAM-less base editor in vivo," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    3. Junhao Fu & Qing Li & Xiaoyu Liu & Tianxiang Tu & Xiujuan Lv & Xidi Yin & Jineng Lv & Zongming Song & Jia Qu & Jinwei Zhang & Jinsong Li & Feng Gu, 2021. "Human cell based directed evolution of adenine base editors with improved efficiency," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    4. Fang Liang & Yu Zhang & Lin Li & Yexin Yang & Ji-Feng Fei & Yanmei Liu & Wei Qin, 2022. "SpG and SpRY variants expand the CRISPR toolbox for genome editing in zebrafish," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    5. Shuo Li & Bo Yuan & Jixin Cao & Jingqi Chen & Jinlong Chen & Jiayi Qiu & Xing-Ming Zhao & Xiaolin Wang & Zilong Qiu & Tian-Lin Cheng, 2020. "Docking sites inside Cas9 for adenine base editing diversification and RNA off-target elimination," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    6. Julian Grünewald & Ronghao Zhou & Sara P. Garcia & Sowmya Iyer & Caleb A. Lareau & Martin J. Aryee & J. Keith Joung, 2019. "Transcriptome-wide off-target RNA editing induced by CRISPR-guided DNA base editors," Nature, Nature, vol. 569(7756), pages 433-437, May.
    7. 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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