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Updated: Oct 20, 2025

Efficient PAM-Less Base Editing for Zebrafish Modeling of Human Genetic Disease with zSpRY-ABE8e
Published on: February 17, 2023
CABE-RY: A PAM-flexible dual-mutation base editor for reliable modeling of multi-nucleotide variants
Wanyu Tao1,2, Qing Liu3, Shisheng Huang1,2
1School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.
Abstract:
Multi-nucleotide variants (MNVs) represent an important type of genetic variation and have biological and clinical significance. To simulate MNVs, we designed four dual-mutation base editors combining hA3A(Y130F), TadA8e(V106W), and protospacer adjacent motif (PAM)-flexible SpRY and selected cytosine and adenine base editor-SpRY (CABE-RY), which had the best editing performance, for further study. Characterization and comparison showed that CABE-RY had a smaller DNA editing window and lower RNA off-target edits than the corresponding single base editors. Thus, we have established a versatile tool to efficiently simulate MNVs over the genome, which could be very useful for functional studies on MNVs in humans.
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