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Science. 2017 Sep 22;357(6357):1303-1307. doi: 10.1126/science.aan4187. Epub 2017 Aug 10.

Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9.

Author information

1
eGenesis, Cambridge, MA 02139, USA.
2
College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
3
State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan Agricultural University, Kunming 650201, China.
4
College of Animal Science and Technology, Yunnan Agricultural University, Kunming 650201, China.
5
Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark.
6
Department of Laboratory Animal Science, College of Basic Medical Sciences, Third Military Medical University, Chongqing, 400038, China.
7
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
8
Research Institute of Shenzhen Jinxinnong Technology, Shenzhen 518106, China.
9
Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA 02138, USA.
10
eGenesis, Cambridge, MA 02139, USA. luhan.yang@egenesisbio.com.

Abstract

Xenotransplantation is a promising strategy to alleviate the shortage of organs for human transplantation. In addition to the concerns about pig-to-human immunological compatibility, the risk of cross-species transmission of porcine endogenous retroviruses (PERVs) has impeded the clinical application of this approach. We previously demonstrated the feasibility of inactivating PERV activity in an immortalized pig cell line. We now confirm that PERVs infect human cells, and we observe the horizontal transfer of PERVs among human cells. Using CRISPR-Cas9, we inactivated all of the PERVs in a porcine primary cell line and generated PERV-inactivated pigs via somatic cell nuclear transfer. Our study highlights the value of PERV inactivation to prevent cross-species viral transmission and demonstrates the successful production of PERV-inactivated animals to address the safety concern in clinical xenotransplantation.

PMID:
28798043
PMCID:
PMC5813284
DOI:
10.1126/science.aan4187
[Indexed for MEDLINE]
Free PMC Article

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