Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9

Science. 2017 Aug 10. pii: eaan4187. doi: 10.1126/science.aan4187. [Epub ahead of print]
Authors
Niu D1,2, Wei HJ3,4, Lin L5, George H1, Wang T1, Lee IH1, Zhao HY3, Wang Y6, Kan Y1, Shrock E7, Lesha E1, Wang G1, Luo Y5, Qing Y3,4, Jiao D3,4, Zhao H3,4, Zhou X6, Wang S8, Wei H6, Güell M1, Church GM1,7,9, Yang L10.
09-27-2017
12:00pm
PST
Categories
RNA Modification & Editing
Speaker
Maryia Barnett
Abstract
Xenotransplantation is a promising strategy to alleviate the shortage of organs for human transplantation. In addition to the concern on pig-to-human immunological compatibility, the risk of cross-species transmission of porcine endogenous retroviruses (PERVs) has impeded the clinical application of this approach. Earlier, we demonstrated the feasibility of inactivating PERV activity in an immortalized pig cell line. Here, we confirmed that PERVs infect human cells, and observed the horizontal transfer of PERVs among human cells. Using CRISPR-Cas9, we inactivated all the PERVs in a porcine primary cell line and generated PERV-inactivated pigs via somatic cell nuclear transfer. Our study highlighted the value of PERV inactivation to prevent cross-species viral transmission and demonstrated the successful production of PERV-inactivated animals to address the safety concern in clinical xenotransplantation.