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Enzymatic conversion of human blood group A kidneys to universal blood group O

Author

Listed:
  • Serena MacMillan

    (University of Cambridge)

  • Sarah A. Hosgood

    (University of Cambridge)

  • Léonie Walker-Panse

    (University of Cambridge)

  • Peter Rahfeld

    (Avivo Biomedical Inc.
    University of British Columbia)

  • Spence S. Macdonald

    (Avivo Biomedical Inc.
    University of British Columbia)

  • Jayachandran N. Kizhakkedathu

    (University of British Columbia
    University of British Columbia)

  • Stephen G. Withers

    (University of British Columbia)

  • Michael L. Nicholson

    (University of Cambridge)

Abstract

ABO blood group compatibility restrictions present the first barrier to donor-recipient matching in kidney transplantation. Here, we present the use of two enzymes, FpGalNAc deacetylase and FpGalactosaminidase, from the bacterium Flavonifractor plautii to enzymatically convert blood group A antigens from the renal vasculature of human kidneys to ‘universal’ O-type. Using normothermic machine perfusion (NMP) and hypothermic machine perfusion (HMP) strategies, we demonstrate blood group A antigen loss of approximately 80% in as little as 2 h NMP and HMP. Furthermore, we show that treated kidneys do not bind circulating anti-A antibodies in an ex vivo model of ABO-incompatible transplantation and do not activate the classical complement pathway. This strategy presents a solution to the donor organ shortage crisis with the potential for direct clinical translation to reduce waiting times for patients with end stage renal disease.

Suggested Citation

  • Serena MacMillan & Sarah A. Hosgood & Léonie Walker-Panse & Peter Rahfeld & Spence S. Macdonald & Jayachandran N. Kizhakkedathu & Stephen G. Withers & Michael L. Nicholson, 2024. "Enzymatic conversion of human blood group A kidneys to universal blood group O," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47131-9
    DOI: 10.1038/s41467-024-47131-9
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