3 years ago

Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9

Marc Güell, Hong-Jiang Wei, Yubo Qing, Emal Lesha, I-Hsiu Lee, Xiaoyang Zhou, Gang Wang, Hong-Ye Zhao, Deling Jiao, Haydy George, Lin Lin, George M. Church, Heng Zhao, Yinan Kan, Dong Niu, Luhan Yang, Hong Wei, Tao Wang, Shouqi Wang, Yonglun Luo, Ellen Shrock, Yong Wang

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.

Publisher URL: http://science.sciencemag.org/cgi/content/short/357/6357/1303

DOI: 10.1126/science.aan4187

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