First-in-Human, Open-Label, Within-Patient Controlled Study to Evaluate an Extensively Humanized Porcine Donor

First-in-Human, Open-Label, Within-Patient Controlled Study to Evaluate an Extensively Humanized Porcine Donor | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article First-in-Human, Open-Label, Within-Patient Controlled Study to Evaluate an Extensively Humanized Porcine Donor hui xie, Li-Jin Zou, Hao Yin, Zhen-Xing Wang, Fan Yang, You-Lai Zhang, and 16 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7042454/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Recent human decedent model studies and compassionate xenograft use have explored the promise of porcine organs for human transplantation. To proceed to human studies, a clinically ready porcine donor must be engineered and its xenograft successfully tested in nonhuman primates. Here we describe the design, creation, and long-term life-supporting function of organs from selectively germline genome-edited pigs (SGGEP) with 11 genomic modifications. These modifications eliminated glycan xenoantigens, overexpressed human transgenes, and enhanced immunological and coagulation compatibility with human biology. In vitro analyses showed SGGEP cells possessed immunological tolerance and coagulation compatibility similar to human cells. In nonhuman primate models, kidney grafts sustained function for 447 days, and cardiac grafts survived healthily for at least 160 days. Skin grafts demonstrated life-supporting capabilities in a lethal skin removal model, facilitating complete wound closure and promoting autologous skin regeneration, remaining viable for ≥25 days without immune suppression. A clinical trial involving 31 patients with thermal burns showed that SGGEP skin grafts achieved complete and durable wound closure, with three cases not requiring autografting. These findings underscore the potential of SGGEP xenotransplantation in addressing donor organ scarcity and highlight the "one pig fits all" strategy as a promising solution for broader applications in human transplantation. Biological sciences/Biological techniques/Genetic engineering Health sciences/Diseases/Skin diseases Full Text Additional Declarations Yes there is potential Competing Interest. G.W. is one of inventors on patents and patents applications related to this article. F.Y. and G.W. owned the share of Gene Heal Pharma, a privately owned company developing therapeutic xenotransplant. All others have no potential conflict of interest. Supplementary Files SupplementalAppendix.docx Supplemental Appendix Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7042454","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":489834555,"identity":"4544f8d4-6064-4578-b0a3-c169d8cc191e","order_by":0,"name":"hui 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