Multiple Human Transgenes Prolong Survival of Triple-Carbohydrate Knockout Porcine Kidney Xenografts in Nonhuman Primates

Genetically modi�ed pigs are being developed to address the critical shortage of human organs for transplantation. We have previously demonstrated signi�cantly prolonged survival of porcine xenografts devoid of three major carbohydrate xenoantigens (3KO) by incorporating human transgenes (HTGs). However, the optimal HTG combination and the mechanisms underlying improved xenograft survival following such genetic editing remain unde�ned. In the current study, we evaluated, in nonhuman primates, immune responses and transplant outcome of 3KO kidney xenografts with or without four different combinations of HTGs. We show that addition of HTGs signi�cantly reduced transcripts associated with initial immune activation, resulting in markedly extended survival of the 3KO xenografts. Most notably, the addition of anti-inammatory genes, TNFAIP3 and HMOX1, was associated with improved graft survival with signi�cantly lower expression of rejection-related gene sets in protocol xenograft biopsies, while the inclusion of coagulation-related HTGs was less effective. Although further studies are needed to de�ne the optimal HTG combination for human recipients, we conclude that multiple combinations of HTGs can effectively prolong primate survival following 3KO kidney xenotransplantation.

• Publication year

  2025

• Venue

  American Journal of Transplantation

• Publication date

  2025-08-01

• Fields of study

  Not labeled

• Identifiers
  DOI 10.1016/j.ajt.2025.07.341
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar

• No claims are published for this paper.

• No concepts are published for this paper.

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