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Nonetheless, a formidable challenge lies in overcoming the rejection of porcine organs by the human immune system. In this study, we generated a six\u2010gene\u2010edited pig model by simultaneously knocking out three major xenoantigens, GGTA1, CMAH, and \u03b24GalNT2, along with the incorporation of coagulation regulatory factor THBD, and two complement regulatory proteins, hCD55 and hCD46, in Bama miniature pigs. These pigs exhibit genetic modifications designed to reduce xenograft rejection while maintaining normal physiology. Assessments of vital organ structure and function, including the heart, liver, spleen, lungs, and kidneys in the gene\u2010edited pigs, showed no abnormalities. The pigs with human transgene knock\u2010in THBD and complement genes exhibited no significant alterations in coagulation function and immune performance. These healthy features hold promise for further xenotransplantation. In conclusion, we successfully constructed six\u2010gene\u2010edited miniature pigs. This work serves as a valuable reference for gene editing strategies for xenotransplantation pig models.<\/jats:p>","DOI":"10.1002\/biot.70030","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T08:16:13Z","timestamp":1747296973000},"source":"Crossref","is-referenced-by-count":7,"title":["Evaluation of Physiological Integrity in Six\u2010Gene\u2010Edited Bama Miniature Pigs as a Model for Xenotransplantation"],"prefix":"10.1002","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-0538-9083","authenticated-orcid":false,"given":"Wen Chuan","family":"Peng","sequence":"first","affiliation":[{"name":"College of Animal Science and Technology Key Laboratory of Animal Genetics Breeding and Reproduction of Shaanxi Province Northwest A&amp;F University  Yangling Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan Yuan","family":"Zhai","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology Key Laboratory of Animal Genetics Breeding and Reproduction of Shaanxi Province Northwest A&amp;F University  Yangling Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng Ke","family":"Li","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology Key Laboratory of Animal Genetics Breeding and Reproduction of Shaanxi Province Northwest A&amp;F University  Yangling Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chu Xiong","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology Key Laboratory of Animal Genetics Breeding and Reproduction of Shaanxi Province Northwest A&amp;F University  Yangling Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia Xiang","family":"Du","sequence":"additional","affiliation":[{"name":"Chengdu Clonorgan Biotechnology Co., Ltd  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan Yan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Chengdu Clonorgan Biotechnology Co., Ltd  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deng Ke","family":"Pan","sequence":"additional","affiliation":[{"name":"Chengdu Clonorgan Biotechnology Co., Ltd  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang Wei","family":"Wu","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology Key Laboratory of Animal Genetics Breeding and Reproduction of Shaanxi Province Northwest A&amp;F University  Yangling Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2120238"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-022-00624-6"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-01896-y"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.16095"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.tp.0000181397.41143.fa"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.12744"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.849711"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.844632"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1707173"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199711150-00005"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2008.02210.x"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-200101150-00021"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e3182a95cbc"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2016.08.035"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11138"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/xen.12213"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02471-9"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2018.03.006"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.16930"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1262\/jrd.2016-079"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2018.03.055"},{"issue":"11","key":"e_1_2_9_23_1","first-page":"2281","article-title":"Genome Engineering Using the CRISPR\u2010Cas9 System","volume":"8","author":"Ran F. 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