Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9

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• dc.contributor.author Niu, Dong
• dc.contributor.author Wei, Hong-Jiang
• dc.contributor.author Lin, Lin
• dc.contributor.author George, Haydy
• dc.contributor.author Wang, Tao
• dc.contributor.author Lee, I-Hsiu
• dc.contributor.author Zhao, Hong-Ye
• dc.contributor.author Wang, Yong
• dc.contributor.author Kan, Yinan
• dc.contributor.author Shrock, Ellen
• dc.contributor.author Lesha, Emal
• dc.contributor.author Wang, Gang
• dc.contributor.author Luo, Yonglun
• dc.contributor.author Qing, Yubo
• dc.contributor.author Jiao, Deling
• dc.contributor.author Zhao, Heng
• dc.contributor.author Zhou, Xiaoyang
• dc.contributor.author Wang, Shouqi
• dc.contributor.author Wei, Hong-Jiang
• dc.contributor.author Güell Cargol, Marc, 1982-
• dc.contributor.author Church, George M.
• dc.contributor.author Yang, Luhan
• dc.date.accessioned 2018-11-14T14:34:30Z
• dc.date.available 2018-11-14T14:34:30Z
• dc.date.issued 2017
• dc.description.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.
• dc.description.sponsorship This study is mainly funded by eGenesis Inc. and was funded by NIH grant P50 HG005550. Y.L. was funded by Danish Research Council for Independent Research (DFF-1337-00128) and Sapere Aude Young Research Talent Prize (DFF-1335-00763). M.G. was funded by a Human Frontiers Science Program Long Term fellowship. Some of the pig production was funded by Major Program on Basic Research Projects of Yunnan Province, China (Grant No. 2014FC006). PERV elements genotyping illumina miseq data have been uploaded to the European Nucleotide Archive (ENA) hosted by the European Bioinformatics Institute (EBI) with the submission reference PRJEB11222
• dc.format.mimetype application/pdf
• dc.identifier.citation Niu D, Wei HJ, Lin L, George H, Wang T, Lee IH et al. Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9. Science. 2017 Sep 22;357(6357):1303-7. DOI: 10.1126/science.aan4187
• dc.identifier.doi http://dx.doi.org/10.1126/science.aan4187
• dc.identifier.issn 0036-8075
• dc.identifier.uri http://hdl.handle.net/10230/35752
• dc.language.iso eng
• dc.publisher American Association for the Advancement of Science (AAAS)
• dc.relation.ispartof Science. 2017 Sep 22;357(6357):1303-7
• dc.rights This is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Science on Vol. 357 Issue 6357, 22 Sep 2017. DOI: 10.1126/science.aan4187
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.subject.other Xenotrasplantament
• dc.subject.other Malalties transmissibles
• dc.subject.other Silenciament gènic
• dc.title Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/acceptedVersion