Highly efficient RNA-guided base editing in rabbit

Nature Communications
Zhiquan LiuZhanjun Li

Abstract

Cytidine base editors (CBEs) and adenine base editors (ABEs), composed of a cytidine deaminase or an evolved adenine deaminase fused to Cas9 nickase, enable the conversion of C·G to T·A or A·T to G·C base pair in organisms, respectively. Here, we show that BE3 and ABE7.10 systems can achieve a targeted mutation efficiency of 53-88% and 44-100%, respectively, in both blastocysts and Founder (F0) rabbits. Meanwhile, this strategy can be used to precisely mimic human pathologies by efficiently inducing nonsense or missense mutations as well as RNA mis-splicing in rabbit. In addition, the reduced frequencies of indels with higher product purity are also determined in rabbit blastocysts by BE4-Gam, which is an updated version of the BE3 system. Collectively, this work provides a simple and efficient method for targeted point mutations and generation of disease models in rabbit.

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Citations

Jul 28, 2018·Plant Biotechnology Journal·Kai HuaJian-Kang Zhu
Apr 19, 2019·The CRISPR Journal·Bei YangJia Chen
May 10, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Zhiquan LiuZhanjun Li
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Datasets Mentioned

BETA
SRP151162

Methods Mentioned

BETA
targeted mutation
gene knockouts
deamination
PCR
genotyping

Software Mentioned

BE3
BE4
Graphpad prism
Gam
Founder
EditR

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