Progressive genetic modifications of porcine cardiac xenografts extend survival to 9 months

Xenotransplantation. 2022 May;29(3):e12744. doi: 10.1111/xen.12744. Epub 2022 Mar 31.


We report orthotopic (life-supporting) survival of genetically engineered porcine cardiac xenografts (with six gene modifications) for almost 9 months in baboon recipients. This work builds on our previously reported heterotopic cardiac xenograft (three gene modifications) survival up to 945 days with an anti-CD40 monoclonal antibody-based immunosuppression. In this current study, life-supporting xenografts containing multiple human complement regulatory, thromboregulatory, and anti-inflammatory proteins, in addition to growth hormone receptor knockout (KO) and carbohydrate antigen KOs, were transplanted in the baboons. Selective "multi-gene" xenografts demonstrate survival greater than 8 months without the requirement of adjunctive medications and without evidence of abnormal xenograft thickness or rejection. These data demonstrate that selective "multi-gene" modifications improve cardiac xenograft survival significantly and may be foundational for paving the way to bridge transplantation in humans.

Keywords: CRISPR; cardiac xenotransplantation; heart failure; pig heart; xenotransplantation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Graft Rejection*
  • Graft Survival
  • Heart Transplantation*
  • Heterografts
  • Humans
  • Immunosuppressive Agents
  • Papio
  • Swine
  • Transplantation, Heterologous


  • Immunosuppressive Agents