IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-49943-1.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-49943-1
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-49943-1?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Shuqian Zhang & Bo Yuan & Jixin Cao & Liting Song & Jinlong Chen & Jiayi Qiu & Zilong Qiu & Xing-Ming Zhao & Jingqi Chen & Tian-Lin Cheng, 2023. "TadA orthologs enable both cytosine and adenine editing of base editors," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    2. Shuqian Zhang & Liting Song & Bo Yuan & Cheng Zhang & Jixin Cao & Jinlong Chen & Jiayi Qiu & Yilin Tai & Jingqi Chen & Zilong Qiu & Xing-Ming Zhao & Tian-Lin Cheng, 2023. "TadA reprogramming to generate potent miniature base editors with high precision," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    3. Nathan Bamidele & Han Zhang & Xiaolong Dong & Haoyang Cheng & Nicholas Gaston & Hailey Feinzig & Hanbing Cao & Karen Kelly & Jonathan K. Watts & Jun Xie & Guangping Gao & Erik J. Sontheimer, 2024. "Domain-inlaid Nme2Cas9 adenine base editors with improved activity and targeting scope," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    4. Emily Zhang & Monica E. Neugebauer & Nicholas A. Krasnow & David R. Liu, 2024. "Phage-assisted evolution of highly active cytosine base editors with enhanced selectivity and minimal sequence context preference," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    5. Ju-Chan Park & Yun-Jeong Kim & Gue-Ho Hwang & Chan Young Kang & Sangsu Bae & Hyuk-Jin Cha, 2024. "Enhancing genome editing in hPSCs through dual inhibition of DNA damage response and repair pathways," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    6. Mu Li & Aaron Zhong & Youjun Wu & Mega Sidharta & Michael Beaury & Xiaolan Zhao & Lorenz Studer & Ting Zhou, 2022. "Transient inhibition of p53 enhances prime editing and cytosine base-editing efficiencies in human pluripotent stem cells," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    7. Elliot H. Choi & Susie Suh & Andrzej T. Foik & Henri Leinonen & Gregory A. Newby & Xin D. Gao & Samagya Banskota & Thanh Hoang & Samuel W. Du & Zhiqian Dong & Aditya Raguram & Sajeev Kohli & Seth Blac, 2022. "In vivo base editing rescues cone photoreceptors in a mouse model of early-onset inherited retinal degeneration," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    8. 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.
    9. Huawei Tong & Haoqiang Wang & Xuchen Wang & Nana Liu & Guoling Li & Danni Wu & Yun Li & Ming Jin & Hengbin Li & Yinghui Wei & Tong Li & Yuan Yuan & Linyu Shi & Xuan Yao & Yingsi Zhou & Hui Yang, 2024. "Development of deaminase-free T-to-S base editor and C-to-G base editor by engineered human uracil DNA glycosylase," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    10. Panagiotis Antoniou & Giulia Hardouin & Pierre Martinucci & Giacomo Frati & Tristan Felix & Anne Chalumeau & Letizia Fontana & Jeanne Martin & Cecile Masson & Megane Brusson & Giulia Maule & Marion Ro, 2022. "Base-editing-mediated dissection of a γ-globin cis-regulatory element for the therapeutic reactivation of fetal hemoglobin expression," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    11. Jianli Tao & Qi Wang & Carlos Mendez-Dorantes & Kathleen H. Burns & Roberto Chiarle, 2022. "Frequency and mechanisms of LINE-1 retrotransposon insertions at CRISPR/Cas9 sites," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    12. Jiaoyang Liao & Shuanghong Chen & Shenlin Hsiao & Yanhong Jiang & Yang Yang & Yuanjin Zhang & Xin Wang & Yongrong Lai & Daniel E. Bauer & Yuxuan Wu, 2023. "Therapeutic adenine base editing of human hematopoietic stem cells," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    13. Ronghao Chen & Yu Cao & Yajing Liu & Dongdong Zhao & Ju Li & Zhihui Cheng & Changhao Bi & Xueli Zhang, 2023. "Enhancement of a prime editing system via optimal recruitment of the pioneer transcription factor P65," Nature Communications, Nature, vol. 14(1), pages 1-8, December.
    14. Xiangfeng Kong & Hainan Zhang & Guoling Li & Zikang Wang & Xuqiang Kong & Lecong Wang & Mingxing Xue & Weihong Zhang & Yao Wang & Jiajia Lin & Jingxing Zhou & Xiaowen Shen & Yinghui Wei & Na Zhong & W, 2023. "Engineered CRISPR-OsCas12f1 and RhCas12f1 with robust activities and expanded target range for genome editing," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    15. Jian Wang & Yuxi Teng & Ruihua Zhang & Yifei Wu & Lei Lou & Yusong Zou & Michelle Li & Zhong-Ru Xie & Yajun Yan, 2021. "Engineering a PAM-flexible SpdCas9 variant as a universal gene repressor," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    16. You-Jeong Kim & Dayoung Yun & Jungjoon K. Lee & Cheulhee Jung & Aram J. Chung, 2024. "Highly efficient CRISPR-mediated genome editing through microfluidic droplet cell mechanoporation," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    17. Mohsin Badat & Ayesha Ejaz & Peng Hua & Siobhan Rice & Weijiao Zhang & Lance D. Hentges & Christopher A. Fisher & Nicholas Denny & Ron Schwessinger & Nirmani Yasara & Noemi B. A. Roy & Fadi Issa & And, 2023. "Direct correction of haemoglobin E β-thalassaemia using base editors," Nature Communications, Nature, vol. 14(1), pages 1-7, December.
    18. Yi-Li Feng & Qian Liu & Ruo-Dan Chen & Si-Cheng Liu & Zhi-Cheng Huang & Kun-Ming Liu & Xiao-Ying Yang & An-Yong Xie, 2022. "DNA nicks induce mutational signatures associated with BRCA1 deficiency," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    19. Michael Kosicki & Felicity Allen & Frances Steward & Kärt Tomberg & Yangyang Pan & Allan Bradley, 2022. "Cas9-induced large deletions and small indels are controlled in a convergent fashion," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    20. 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.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49943-1. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.