{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T07:03:36Z","timestamp":1791875016737,"version":"4.3.4"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,8,26]],"date-time":"2024-08-26T00:00:00Z","timestamp":1724630400000},"content-version":"vor","delay-in-days":56,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2019YFA0110700"],"award-info":[{"award-number":["2019YFA0110700"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Xenotransplantation"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The number of multigene\u2010modified donor pigs for xenotransplantation is increasing with the advent of gene\u2010editing technologies. However, it remains unclear which gene combination is suitable for specific\u00a0organ transplantation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this study, we utilized CRISPR\/Cas9 gene editing technology, piggyBac transposon system, and somatic cell cloning to construct GTKO\/hCD55\/hTBM\/hCD39 four\u2010gene\u2010edited cloned (GEC) pigs and performed kidney transplantation from pig to rhesus monkey to evaluate the effectiveness of these GEC pigs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>First, 107 cell colonies were obtained through drug selection, of which seven were 4\u2010GE colonies. Two colonies were selected for somatic cell nuclear transfer (SCNT), resulting in seven fetuses, of which four were GGTA1 biallelic knockout. Out of these four, two fetuses had higher expression of hCD55, hTBM, and hCD39. Therefore, these two fetuses were selected for two consecutive rounds of cloning, resulting in 97 live piglets. After phenotype identification, the GGTA1 gene of these pigs was inactivated, and hCD55, hTBM, and hCD39 were expressed in cells and multiple tissues. Furthermore, the numbers of monkey IgM and IgG binding to the peripheral blood mononuclear cells (PBMCs) of the 4\u2010GEC pigs were markedly reduced. Moreover, 4\u2010GEC porcine PBMCs had greater survival rates than those from wild\u2010type pigs through complement\u2010mediated cytolysis assays. In pig\u2010to\u2010monkey kidney xenotransplantation, the kidney xenograft successfully survived for 11 days. All physiological and biochemical indicators were normal, and no hyperacute rejection or coagulation abnormalities were found after transplantation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These results indicate that the GTKO\/hCD55\/hTBM\/hCD39 four\u2010gene modification effectively alleviates immune rejection, and the pig kidney can functionally support the recipient monkey's life.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/xen.12881","type":"journal-article","created":{"date-parts":[[2024,8,26]],"date-time":"2024-08-26T07:54:13Z","timestamp":1724658853000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Production of Four\u2010Gene (GTKO\/hCD55\/hTBM\/hCD39)\u2010Edited Donor Pigs and Kidney Xenotransplantation"],"prefix":"10.1111","volume":"31","author":[{"given":"Chang","family":"Yang","sequence":"first","affiliation":[{"name":"Yunnan Province Key Laboratory for Porcine Gene Editing and Xenotransplantation Yunnan Agricultural University Kunming China"},{"name":"Yunnan Province Xenotransplantation Research Engineering Center Yunnan Agricultural University Kunming China"},{"name":"Faculty of Animal Science and Technology Yunnan Agricultural University Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunfang","family":"Wei","sequence":"additional","affiliation":[{"name":"Yunnan Province Key Laboratory for Porcine Gene Editing and Xenotransplantation Yunnan Agricultural University Kunming China"},{"name":"Yunnan Province Xenotransplantation Research Engineering Center Yunnan Agricultural University Kunming China"},{"name":"Faculty of Animal Science and Technology Yunnan Agricultural University Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinglong","family":"Li","sequence":"additional","affiliation":[{"name":"Yunnan Province Key Laboratory for Porcine Gene Editing and Xenotransplantation Yunnan Agricultural University Kunming China"},{"name":"Yunnan Province Xenotransplantation Research Engineering Center Yunnan Agricultural University Kunming China"},{"name":"Faculty of Animal Science and Technology Yunnan Agricultural University Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaixiang","family":"Xu","sequence":"additional","affiliation":[{"name":"Yunnan Province Key Laboratory for Porcine Gene Editing and Xenotransplantation Yunnan Agricultural University Kunming China"},{"name":"Yunnan Province Xenotransplantation Research Engineering Center Yunnan Agricultural University Kunming China"},{"name":"College of Veterinary Medicine Yunnan Agricultural University Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoying","family":"Huo","sequence":"additional","affiliation":[{"name":"Yunnan Province Key Laboratory for Porcine Gene Editing and Xenotransplantation Yunnan Agricultural University Kunming China"},{"name":"Yunnan Province Xenotransplantation Research Engineering Center Yunnan Agricultural University Kunming China"},{"name":"College of Veterinary Medicine Yunnan Agricultural University Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0574-9785","authenticated-orcid":false,"given":"Gang","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Organ Transplantation Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Yunnan Province Key Laboratory for Porcine Gene Editing and Xenotransplantation Yunnan Agricultural University Kunming China"},{"name":"Yunnan Province Xenotransplantation Research Engineering Center Yunnan Agricultural University Kunming China"},{"name":"College of Veterinary Medicine Yunnan Agricultural University Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaoxiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Yunnan Province Key Laboratory for Porcine Gene Editing and Xenotransplantation Yunnan Agricultural University Kunming China"},{"name":"Yunnan Province Xenotransplantation Research Engineering Center Yunnan Agricultural University Kunming China"},{"name":"Faculty of Animal Science and Technology Yunnan Agricultural University Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taiyun","family":"Wei","sequence":"additional","affiliation":[{"name":"Yunnan Province Key Laboratory for Porcine Gene Editing and Xenotransplantation Yunnan Agricultural University Kunming China"},{"name":"Yunnan Province Xenotransplantation Research Engineering Center Yunnan Agricultural University Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yubo","family":"Qing","sequence":"additional","affiliation":[{"name":"Yunnan Province Key Laboratory for Porcine Gene Editing and Xenotransplantation Yunnan Agricultural University Kunming China"},{"name":"Yunnan Province Xenotransplantation Research Engineering Center Yunnan Agricultural University Kunming China"},{"name":"College of Veterinary Medicine Yunnan Agricultural University Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxiong","family":"Guo","sequence":"additional","affiliation":[{"name":"Yunnan Province Key Laboratory for Porcine Gene Editing and Xenotransplantation Yunnan Agricultural University Kunming China"},{"name":"Yunnan Province Xenotransplantation Research Engineering Center Yunnan Agricultural University Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongfang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Yunnan Province Key Laboratory for Porcine Gene Editing and Xenotransplantation Yunnan Agricultural University Kunming China"},{"name":"Yunnan Province Xenotransplantation Research Engineering Center Yunnan Agricultural University Kunming China"},{"name":"Faculty of Animal Science and Technology Yunnan Agricultural University Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Yunnan Province Key Laboratory for Porcine Gene Editing and Xenotransplantation Yunnan Agricultural University Kunming China"},{"name":"Yunnan Province Xenotransplantation Research Engineering Center Yunnan Agricultural University Kunming China"},{"name":"Faculty of Animal Science and Technology Yunnan Agricultural University Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deling","family":"Jiao","sequence":"additional","affiliation":[{"name":"Yunnan Province Key Laboratory for Porcine Gene Editing and Xenotransplantation Yunnan Agricultural University Kunming China"},{"name":"Yunnan Province Xenotransplantation Research Engineering Center Yunnan Agricultural University Kunming China"},{"name":"College of Veterinary Medicine Yunnan Agricultural University Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Xiong","sequence":"additional","affiliation":[{"name":"Yunnan Province Key Laboratory for Porcine Gene Editing and Xenotransplantation Yunnan Agricultural University Kunming China"},{"name":"Yunnan Province Xenotransplantation Research Engineering Center Yunnan Agricultural University Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Ameen","family":"Jamal","sequence":"additional","affiliation":[{"name":"Yunnan Province Key Laboratory for Porcine Gene Editing and Xenotransplantation Yunnan Agricultural University Kunming China"},{"name":"Yunnan Province Xenotransplantation Research Engineering Center Yunnan Agricultural University Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong\u2010Ye","family":"Zhao","sequence":"additional","affiliation":[{"name":"Yunnan Province Key Laboratory for Porcine Gene Editing and Xenotransplantation Yunnan Agricultural University Kunming China"},{"name":"Yunnan Province Xenotransplantation Research Engineering Center Yunnan Agricultural University Kunming China"},{"name":"College of Veterinary Medicine Yunnan Agricultural University Kunming 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