Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9

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 applicatio...

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Detalles Bibliográficos
Autores: Niu, Dong, Wei, Hong-Jiang, Lin, Lin, George, Haydy, Wang, Tao, Lee, I-Hsiu, Zhao, Hong-Ye, Wang, Yong, Kan, Yinan, Shrock, Ellen, Lesha, Emal, Wang, Gang, Luo, Yonglun, Qing, Yubo, Jiao, Deling, Zhao, Heng, Zhou, Xiaoyang, Wang, Shouqi, Güell Cargol, Marc, 1982-, Church, George M., Yang, Luhan
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2017
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/35752
Acceso en línea:http://hdl.handle.net/10230/35752
http://dx.doi.org/10.1126/science.aan4187
Access Level:acceso abierto
Palabra clave:Xenotrasplantament
Malalties transmissibles
Silenciament gènic
Descripción
Sumario: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.