TY - JOUR
T1 - Cre-dependent Cas9-expressing pigs enable efficient in vivo genome editing
AU - Wang, Kepin
AU - Jin, Qin
AU - Ruan, Degong
AU - Yang, Yi
AU - Liu, Qishuai
AU - Wu, Han
AU - Zhou, Zhiwei
AU - Ouyang, Zhen
AU - Liu, Zhaoming
AU - Zhao, Yu
AU - Zhao, Bentian
AU - Zhang, Quanjun
AU - Peng, Jiangyun
AU - Lai, Chengdan
AU - Fan, Nana
AU - Liang, Yanhui
AU - Lan, Ting
AU - Li, Nan
AU - Wang, Xiaoshan
AU - Wang, Xinlu
AU - Fan, Yong
AU - Doevendans, Pieter A.
AU - Sluijter, Joost P.G.
AU - Liu, Pentao
AU - Li, Xiaoping
AU - Lai, Liangxue
N1 - Funding Information:
This work was supported by grants from the National Natural Science Foundation of China (81672317, 81671121, 31601187, 31401271), the Bureau of International Cooperation, The Chinese Academy of Sciences (154144KYSB20150033), the Science and Technology Planning Project of Guangdong Province, China (2013B060300017, 2014B020225003, 2014B030301058, 2015A0 30310119, 2016A020216023, 2016B030229006), and the Bureau of Science and Technology of Guangzhou Municipality (201505011111498).
Publisher Copyright:
© 2017 Wang et al.
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85037673870&partnerID=8YFLogxK
U2 - 10.1101/gr.222521.117
DO - 10.1101/gr.222521.117
M3 - Article
C2 - 29146772
AN - SCOPUS:85037673870
SN - 1088-9051
VL - 27
SP - 2061
EP - 2071
JO - Genome Research
JF - Genome Research
IS - 12
ER -