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...
| Autores: | , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | artículo |
| Estado: | Versión aceptada para publicación |
| Fecha de publicación: | 2017 |
| País: | España |
| Recursos: | Universitat Pompeu Fabra |
| Repositorio: | Repositorio Digital de la UPF |
| OAI Identifier: | oai:repositori.upf.edu:10230/35752 |
| Acesso em linha: | http://hdl.handle.net/10230/35752 http://dx.doi.org/10.1126/science.aan4187 |
| Access Level: | acceso abierto |
| Palavra-chave: | Xenotrasplantament Malalties transmissibles Silenciament gènic |
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Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9Niu, DongWei, Hong-JiangLin, LinGeorge, HaydyWang, TaoLee, I-HsiuZhao, Hong-YeWang, YongKan, YinanShrock, EllenLesha, EmalWang, GangLuo, YonglunQing, YuboJiao, DelingZhao, HengZhou, XiaoyangWang, ShouqiWei, Hong-JiangGüell Cargol, Marc, 1982-Church, George M.Yang, LuhanXenotrasplantamentMalalties transmissiblesSilenciament gènicXenotransplantation 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.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 PRJEB11222American Association for the Advancement of Science (AAAS)201820182017info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/35752http://dx.doi.org/10.1126/science.aan4187reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésScience. 2017 Sep 22;357(6357):1303-7This 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.aan4187info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/357522026-06-12T07:21:37Z |
| dc.title.none.fl_str_mv |
Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9 |
| title |
Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9 |
| spellingShingle |
Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9 Niu, Dong Xenotrasplantament Malalties transmissibles Silenciament gènic |
| title_short |
Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9 |
| title_full |
Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9 |
| title_fullStr |
Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9 |
| title_full_unstemmed |
Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9 |
| title_sort |
Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9 |
| dc.creator.none.fl_str_mv |
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 Wei, Hong-Jiang Güell Cargol, Marc, 1982- Church, George M. Yang, Luhan |
| author |
Niu, Dong |
| author_facet |
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 |
| author_role |
author |
| author2 |
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 |
| author2_role |
author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Xenotrasplantament Malalties transmissibles Silenciament gènic |
| topic |
Xenotrasplantament Malalties transmissibles Silenciament gènic |
| description |
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. |
| publishDate |
2017 |
| dc.date.none.fl_str_mv |
2017 2018 2018 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion |
| format |
article |
| status_str |
acceptedVersion |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10230/35752 http://dx.doi.org/10.1126/science.aan4187 |
| url |
http://hdl.handle.net/10230/35752 http://dx.doi.org/10.1126/science.aan4187 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Science. 2017 Sep 22;357(6357):1303-7 |
| dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf application/pdf |
| dc.publisher.none.fl_str_mv |
American Association for the Advancement of Science (AAAS) |
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American Association for the Advancement of Science (AAAS) |
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reponame:Repositorio Digital de la UPF instname:Universitat Pompeu Fabra |
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Universitat Pompeu Fabra |
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Repositorio Digital de la UPF |
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Repositorio Digital de la UPF |
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15,812429 |