Highly efficient RNA-guided base editing in rabbit

Zhiquan Liu, Mao Chen, Siyu Chen, Jichao Deng, Yuning Song, Liangxue Lai () and Zhanjun Li ()
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Zhiquan Liu: Jilin University
Mao Chen: Jilin University
Siyu Chen: Jilin University
Jichao Deng: Jilin University
Yuning Song: Jilin University
Liangxue Lai: Jilin University
Zhanjun Li: Jilin University

Nature Communications, 2018, vol. 9, issue 1, 1-10

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-05232-2

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