PUBLICATION

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

Authors
Qin, W., Liang, F., Lin, S.J., Petree, C., Huang, K., Zhang, Y., Li, L., Varshney, P., Mourrain, P., Liu, Y., Varshney, G.K.
ID
ZDB-PUB-240705-12
Date
2024
Source
Nature communications   15: 56135613 (Journal)
Registered Authors
Lin, Sheng-Jia, Liu, Yanmei, Mourrain, Philippe, Varshney, Gaurav
Keywords
none
MeSH Terms
  • Zebrafish*/genetics
  • CRISPR-Cas Systems*
  • Alleles
  • Gene Editing*/methods
  • Adenine*/metabolism
  • INDEL Mutation*
  • Animals
  • RNA, Guide, CRISPR-Cas Systems/genetics
  • RNA, Guide, CRISPR-Cas Systems/metabolism
  • Animals, Genetically Modified
(all 10)
PubMed
38965236 Full text @ Nat. Commun.
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.
Genes / Markers
Figures
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Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
w2
    Point Mutation
    1 - 1 of 1
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    Human Disease / Model
    No data available
    Sequence Targeting Reagents
    1 - 7 of 7
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    Fish
    No data available
    Antibodies
    No data available
    Orthology
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    Engineered Foreign Genes
    No data available
    Mapping
    No data available