PUBLICATION

Cytosine base editors with increased PAM and deaminase motif flexibility for gene editing in zebrafish

Authors
Zhang, Y., Liu, Y., Qin, W., Zheng, S., Xiao, J., Xia, X., Yuan, X., Zeng, J., Shi, Y., Zhang, Y., Ma, H., Varshney, G.K., Fei, J.F., Liu, Y.
ID
ZDB-PUB-241105-1
Date
2024
Source
Nature communications   15: 95269526 (Journal)
Registered Authors
Fei, Jifeng, Liu, Yanmei, Varshney, Gaurav
Keywords
none
MeSH Terms
  • Gene Editing*/methods
  • Nucleotide Motifs
  • Mutation
  • Zebrafish*/genetics
  • CRISPR-Cas Systems*
  • Cytosine*/metabolism
  • DNA/genetics
  • DNA/metabolism
  • Humans
  • Animals
  • Disease Models, Animal
(all 11)
PubMed
39496611 Full text @ Nat. Commun.
Abstract
Cytosine base editing is a powerful tool for making precise single nucleotide changes in cells and model organisms like zebrafish, which are valuable for studying human diseases. However, current base editors struggle to edit cytosines in certain DNA contexts, particularly those with GC and CC pairs, limiting their use in modelling disease-related mutations. Here we show the development of zevoCDA1, an optimized cytosine base editor for zebrafish that improves editing efficiency across various DNA contexts and reduces restrictions imposed by the protospacer adjacent motif. We also create zevoCDA1-198, a more precise editor with a narrower editing window of five nucleotides, minimizing off-target effects. Using these advanced tools, we successfully generate zebrafish models of diseases that were previously challenging to create due to sequence limitations. This work enhances the ability to introduce human pathogenic mutations in zebrafish, broadening the scope for genomic research with improved precision and efficiency.
Genes / Markers
Figures
Figure Gallery (3 images)
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Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
zsc1
    		Point Mutation
    zsc2
      		Point Mutation
      1 - 2 of 2
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      Human Disease / Model
      No data available
      Sequence Targeting Reagents
      Fish
      No data available
      Antibodies
      No data available
      Orthology
      No data available
      Engineered Foreign Genes
      No data available
      Mapping
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      Citation
      Zhang, Y., Liu, Y., Qin, W., Zheng, S., Xiao, J., Xia, X., Yuan, X., Zeng, J., Shi, Y., Zhang, Y., Ma, H., Varshney, G.K., Fei, J.F., Liu, Y. (2024) Cytosine base editors with increased PAM and deaminase motif flexibility for gene editing in zebrafish. Nature communications. 15:95269526.