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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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2017-09, Vol.357 (6357), p.1303-1307 |
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| creator | 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 Güell, Marc Church, George M. Yang, Luhan |
| 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. |
| doi_str_mv | 10.1126/science.aan4187 |
| format | Article |
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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.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.aan4187</identifier><identifier>PMID: 28798043</identifier><language>eng</language><publisher>United States: American Association for the Advancement of Science</publisher><subject>Animals ; CRISPR ; CRISPR-Cas Systems ; Deactivation ; Disease Transmission, Infectious - prevention & control ; Endogenous retroviruses ; Endogenous Retroviruses - genetics ; Feasibility studies ; Gene Editing - methods ; Genome editing ; Genomes ; HEK293 Cells ; Hogs ; Horizontal transfer ; Humans ; Immunology ; Inactivation ; Malalties transmissibles ; Nuclear engineering ; Nuclear safety ; Nuclear transfer ; Organs ; Retroviridae Infections - transmission ; Silenciament gènic ; Somatic cell nuclear transfer ; Sus scrofa - genetics ; Sus scrofa - virology ; Swine ; Tissues ; Transplantation ; Transplantation, Heterologous - adverse effects ; Transplants ; Transplants & implants ; Xenografts ; Xenotransplantation ; Xenotrasplantament</subject><ispartof>Science (American Association for the Advancement of Science), 2017-09, Vol.357 (6357), p.1303-1307</ispartof><rights>Copyright © 2017 by the American Association for the Advancement of Science</rights><rights>Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.</rights><rights>Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works</rights><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 info:eu-repo/semantics/openAccess</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c588t-f534f1ac8b152aeba3a4994724eb3af85e1c51788430acb9d53b5c7cbbd10c243</citedby><cites>FETCH-LOGICAL-c588t-f534f1ac8b152aeba3a4994724eb3af85e1c51788430acb9d53b5c7cbbd10c243</cites><orcidid>0000-0002-7546-4948 ; 0000-0002-3287-4613 ; 0000-0002-4510-6672 ; 0000-0001-6183-6627 ; 0000-0002-0007-7759 ; 0000-0003-4000-7912 ; 0000-0001-7200-7867 ; 0000-0002-8902-3537 ; 0000-0002-0775-2913 ; 0000-0002-0212-4301 ; 0000-0002-5663-1093 ; 0000-0002-5900-3033 ; 0000-0003-3894-7665 ; 0000-0001-7159-4983 ; 0000-0002-9320-5894</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/26399895$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/26399895$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,776,780,799,881,2871,2872,26951,27901,27902,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28798043$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Niu, Dong</creatorcontrib><creatorcontrib>Wei, Hong-Jiang</creatorcontrib><creatorcontrib>Lin, Lin</creatorcontrib><creatorcontrib>George, Haydy</creatorcontrib><creatorcontrib>Wang, Tao</creatorcontrib><creatorcontrib>Lee, I-Hsiu</creatorcontrib><creatorcontrib>Zhao, Hong-Ye</creatorcontrib><creatorcontrib>Wang, Yong</creatorcontrib><creatorcontrib>Kan, Yinan</creatorcontrib><creatorcontrib>Shrock, Ellen</creatorcontrib><creatorcontrib>Lesha, Emal</creatorcontrib><creatorcontrib>Wang, Gang</creatorcontrib><creatorcontrib>Luo, Yonglun</creatorcontrib><creatorcontrib>Qing, Yubo</creatorcontrib><creatorcontrib>Jiao, Deling</creatorcontrib><creatorcontrib>Zhao, Heng</creatorcontrib><creatorcontrib>Zhou, Xiaoyang</creatorcontrib><creatorcontrib>Wang, Shouqi</creatorcontrib><creatorcontrib>Wei, Hong</creatorcontrib><creatorcontrib>Güell, Marc</creatorcontrib><creatorcontrib>Church, George M.</creatorcontrib><creatorcontrib>Yang, Luhan</creatorcontrib><title>Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><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.</description><subject>Animals</subject><subject>CRISPR</subject><subject>CRISPR-Cas Systems</subject><subject>Deactivation</subject><subject>Disease Transmission, Infectious - prevention & control</subject><subject>Endogenous retroviruses</subject><subject>Endogenous Retroviruses - genetics</subject><subject>Feasibility studies</subject><subject>Gene Editing - methods</subject><subject>Genome editing</subject><subject>Genomes</subject><subject>HEK293 Cells</subject><subject>Hogs</subject><subject>Horizontal transfer</subject><subject>Humans</subject><subject>Immunology</subject><subject>Inactivation</subject><subject>Malalties transmissibles</subject><subject>Nuclear engineering</subject><subject>Nuclear safety</subject><subject>Nuclear transfer</subject><subject>Organs</subject><subject>Retroviridae Infections - transmission</subject><subject>Silenciament gènic</subject><subject>Somatic cell nuclear transfer</subject><subject>Sus scrofa - genetics</subject><subject>Sus scrofa - virology</subject><subject>Swine</subject><subject>Tissues</subject><subject>Transplantation</subject><subject>Transplantation, Heterologous - adverse effects</subject><subject>Transplants</subject><subject>Transplants & implants</subject><subject>Xenografts</subject><subject>Xenotransplantation</subject><subject>Xenotrasplantament</subject><issn>0036-8075</issn><issn>1095-9203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>XX2</sourceid><recordid>eNpdkc1vEzEQxS1ERdPCmRNoJS69bOuP9dq-IKGIlkiVigqcrVlnNjhK7GDvRuK_x2mW8HGwbOv93tgzj5DXjF4zxtub7DwGh9cAoWFaPSMzRo2sDafiOZlRKtpaUyXPyUXOa0qLZsQLcs61Mpo2YkbuFgHc4Pcw-Biq2Fe7mJwPWGFYxhWGOOYq4ZDi3qdy9KHa-VWuxuzDqpo_Lr58fqznkM1LctbDJuOrab8k324_fp1_qu8f7hbzD_e1k1oPdS9F0zNwumOSA3YgoDGmUbzBTkCvJTInmdK6ERRcZ5ZSdNIp13VLRh1vxCV5f6y7G7stLh2GIcHG7pLfQvppI3j7rxL8d7uKeys1E1wfCrBjAZdHZxM6TA6GJ-PpclicKm6FaBk3xXM1PZrijxHzYLc-O9xsIGAZkGWGa8moUKyg7_5D13FMoYykUKr02nIuC3UzfSLFnBP2pwYYtYdg7RSsnYItjrd_933ifydZgDdHYJ2HmP7orTBGGyl-AVFSqyg</recordid><startdate>20170922</startdate><enddate>20170922</enddate><creator>Niu, Dong</creator><creator>Wei, Hong-Jiang</creator><creator>Lin, Lin</creator><creator>George, Haydy</creator><creator>Wang, Tao</creator><creator>Lee, I-Hsiu</creator><creator>Zhao, Hong-Ye</creator><creator>Wang, Yong</creator><creator>Kan, Yinan</creator><creator>Shrock, Ellen</creator><creator>Lesha, Emal</creator><creator>Wang, Gang</creator><creator>Luo, Yonglun</creator><creator>Qing, Yubo</creator><creator>Jiao, Deling</creator><creator>Zhao, Heng</creator><creator>Zhou, Xiaoyang</creator><creator>Wang, Shouqi</creator><creator>Wei, Hong</creator><creator>Güell, Marc</creator><creator>Church, George M.</creator><creator>Yang, Luhan</creator><general>American Association for the Advancement of Science</general><general>The American Association for the Advancement of Science</general><general>American Association for the Advancement of Science (AAAS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QF</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QQ</scope><scope>7QR</scope><scope>7SC</scope><scope>7SE</scope><scope>7SN</scope><scope>7SP</scope><scope>7SR</scope><scope>7SS</scope><scope>7T7</scope><scope>7TA</scope><scope>7TB</scope><scope>7TK</scope><scope>7TM</scope><scope>7U5</scope><scope>7U9</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>H94</scope><scope>JG9</scope><scope>JQ2</scope><scope>K9.</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>XX2</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-7546-4948</orcidid><orcidid>https://orcid.org/0000-0002-3287-4613</orcidid><orcidid>https://orcid.org/0000-0002-4510-6672</orcidid><orcidid>https://orcid.org/0000-0001-6183-6627</orcidid><orcidid>https://orcid.org/0000-0002-0007-7759</orcidid><orcidid>https://orcid.org/0000-0003-4000-7912</orcidid><orcidid>https://orcid.org/0000-0001-7200-7867</orcidid><orcidid>https://orcid.org/0000-0002-8902-3537</orcidid><orcidid>https://orcid.org/0000-0002-0775-2913</orcidid><orcidid>https://orcid.org/0000-0002-0212-4301</orcidid><orcidid>https://orcid.org/0000-0002-5663-1093</orcidid><orcidid>https://orcid.org/0000-0002-5900-3033</orcidid><orcidid>https://orcid.org/0000-0003-3894-7665</orcidid><orcidid>https://orcid.org/0000-0001-7159-4983</orcidid><orcidid>https://orcid.org/0000-0002-9320-5894</orcidid></search><sort><creationdate>20170922</creationdate><title>Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9</title><author>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 ; Güell, Marc ; Church, George M. ; Yang, Luhan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c588t-f534f1ac8b152aeba3a4994724eb3af85e1c51788430acb9d53b5c7cbbd10c243</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>CRISPR</topic><topic>CRISPR-Cas Systems</topic><topic>Deactivation</topic><topic>Disease Transmission, Infectious - 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| fulltext | fulltext |
| identifier | ISSN: 0036-8075 |
| ispartof | Science (American Association for the Advancement of Science), 2017-09, Vol.357 (6357), p.1303-1307 |
| issn | 0036-8075 1095-9203 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5813284 |
| source | American Association for the Advancement of Science; Jstor Complete Legacy; MEDLINE; Recercat |
| subjects | Animals CRISPR CRISPR-Cas Systems Deactivation Disease Transmission, Infectious - prevention & control Endogenous retroviruses Endogenous Retroviruses - genetics Feasibility studies Gene Editing - methods Genome editing Genomes HEK293 Cells Hogs Horizontal transfer Humans Immunology Inactivation Malalties transmissibles Nuclear engineering Nuclear safety Nuclear transfer Organs Retroviridae Infections - transmission Silenciament gènic Somatic cell nuclear transfer Sus scrofa - genetics Sus scrofa - virology Swine Tissues Transplantation Transplantation, Heterologous - adverse effects Transplants Transplants & implants Xenografts Xenotransplantation Xenotrasplantament |
| title | Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9 |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-07T22%3A45%3A17IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-jstor_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Inactivation%20of%20porcine%20endogenous%20retrovirus%20in%20pigs%20using%20CRISPR-Cas9&rft.jtitle=Science%20(American%20Association%20for%20the%20Advancement%20of%20Science)&rft.au=Niu,%20Dong&rft.date=2017-09-22&rft.volume=357&rft.issue=6357&rft.spage=1303&rft.epage=1307&rft.pages=1303-1307&rft.issn=0036-8075&rft.eissn=1095-9203&rft_id=info:doi/10.1126/science.aan4187&rft_dat=%3Cjstor_pubme%3E26399895%3C/jstor_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1974996225&rft_id=info:pmid/28798043&rft_jstor_id=26399895&rfr_iscdi=true |