Volume 25, No 2, Feb 2015

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 25 Issue 2, February 2015: 258-261

LETTERS TO THE EDITOR

One-step generation of p53 gene biallelic mutant Cynomolgus monkey via the CRISPR/Cas system

Haifeng Wan^1,*, Chunjing Feng^1,2,*, Fei Teng^1,2,*, Shihua Yang^3,4,*, Baoyang Hu¹, Yuyu Niu⁵, Andy Peng Xiang⁶, Weizhen Fang⁷, Weizhi Ji⁵, Wei Li¹, Xiaoyang Zhao¹ and Qi Zhou¹

¹State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
²University of Chinese Academy of Sciences, Beijing 100049, China
³College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong 510642, China
⁴Key Laboratory of Comprehensive Prevention and Control for Severe Clinical Animal Diseases of Guangdong Province, Guangzhou, Guangdong 510642, China
⁵Yunnan Key Laboratory of Primate Biomedical Research, Kunming, Yunnan 650500, China
⁶Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China
⁷Beijing Xieerxin Institute of Biological Resources, Beijing, China Correspondence: Qi Zhou, E-mail: qzhou@ioz.ac.cn; Xiaoyang Zhao, E-mail: xyzhao@ioz.ac.cn; Wei Li,(liwei@ioz.ac.cn)

Non-human primates (NHPs) are genetically, physiologically and psychologically more similar to humans than other model organisms, providing an important model for human development and diseases1,2. Precise genome modification in non-human primates (NHPs) holds great promise for biomedical researches. However, owing to the long sexual maturation time and low reproduction rate of NHPs, it is very challenging to generate biallelic mutant NHPs for loss-of-function studies through breeding. Recently, the site-specific nucleases, namely TALENs (transcription activator-like effector nucleases) and CRISPR (clustered regularly interspaced short palindromic repeat)/Cas (CRISPR-associated) system, make it feasible to generate NHPs with precise genome modifications, yet the resulting transgenic animals exhibited mosaic mutations accompanied by the presence of wild type allele in different tissues3,4. Thus, the feasibility of obtaining biallelic mutations in monkeys remains an open question. Here we report that by systematically optimizing the mutagenesis efficiency of the CRISPR/Cas-based method in monkeys, we have successfully obtained the first live p53 biallelic mutant monkey, and achieved homology directed repair (HDR)-driven gene editing with nucleotide-level precision in monkey embryos.

10.1038/cr.2014.158

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