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
-
- Adenine*/metabolism
- Alleles
- Animals
- Animals, Genetically Modified
- CRISPR-Cas Systems*
- Gene Editing*/methods
- INDEL Mutation*
- RNA, Guide, CRISPR-Cas Systems/genetics
- RNA, Guide, CRISPR-Cas Systems/metabolism
- Zebrafish*/genetics
- PubMed
- 38965236 Full text @ Nat. Commun.
Citation
Qin, W., Liang, F., Lin, S.J., Petree, C., Huang, K., Zhang, Y., Li, L., Varshney, P., Mourrain, P., Liu, Y., Varshney, G.K. (2024) ABE-ultramax for high-efficiency biallelic adenine base editing in zebrafish. Nature communications. 15:56135613.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping