Format

Send to

Choose Destination
Nat Commun. 2018 Jul 13;9(1):2717. doi: 10.1038/s41467-018-05232-2.

Highly efficient RNA-guided base editing in rabbit.

Author information

1
Jilin Provincial Key Laboratory of Animal Embryo Engineering, Institute of Zoonosis, Jilin University, Changchun, 130062, China.
2
Jilin Provincial Key Laboratory of Animal Embryo Engineering, Institute of Zoonosis, Jilin University, Changchun, 130062, China. lai_liangxue@gibh.ac.cn.
3
Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong, 510530, China. lai_liangxue@gibh.ac.cn.
4
Jilin Provincial Key Laboratory of Animal Embryo Engineering, Institute of Zoonosis, Jilin University, Changchun, 130062, China. lizj_1998@jlu.edu.cn.

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.

PMID:
30006570
PMCID:
PMC6045575
DOI:
10.1038/s41467-018-05232-2
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center