期刊
GENOME RESEARCH
卷 27, 期 12, 页码 2061-2071出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gr.222521.117
关键词
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资金
- National Natural Science Foundation of China [81672317, 81671121, 31601187, 31401271]
- Bureau of International Cooperation
- Chinese Academy of Sciences [154144KYSB20150033]
- Science and Technology Planning Project of Guangdong Province, China [2013B060300017, 2014B020225003, 2014B030301058, 2015A030310119, 2016A020216023, 2016B030229006]
- Bureau of Science and Technology of Guangzhou Municipality [201505011111498]
Despite being time-consuming and costly, generating genome-edited pigs holds great promise for agricultural, biomedical, and pharmaceutical applications. To further facilitate genome editing in pigs, we report here establishment of a pig line with Cre-inducible Cas9 expression that allows a variety of ex vivo genome editing in fibroblast cells including single-and multigene modifications, chromosome rearrangements, and efficient in vivo genetic modifications. As a proof of principle, we were able to simultaneously inactivate five tumor suppressor genes (TP53, PTEN, APC, BRCA1, and BRCA2) and activate one oncogene (KRAS), achieved by delivering Cre recombinase and sgRNAs, which caused rapid lung tumor development. The efficient genome editing shown here demonstrates that these pigs can serve as a powerful tool for dissecting in vivo gene functions and biological processes in a temporal manner and for streamlining the production of genome-edited pigs for disease modeling.
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