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
-
- Mutation
- Humans
- Disease Models, Animal
- Nucleotide Motifs
- CRISPR-Cas Systems*
- Gene Editing*/methods
- DNA/genetics
- DNA/metabolism
- Zebrafish*/genetics
- Animals
- Cytosine*/metabolism
- PubMed
- 39496611 Full text @ Nat. Commun.
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.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping