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

Serena MacMillan (), Sarah A. Hosgood, Léonie Walker-Panse, Peter Rahfeld, Spence S. Macdonald, Jayachandran N. Kizhakkedathu, Stephen G. Withers and Michael L. Nicholson ()
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Serena MacMillan: University of Cambridge
Sarah A. Hosgood: University of Cambridge
Léonie Walker-Panse: University of Cambridge
Peter Rahfeld: Avivo Biomedical Inc.
Spence S. Macdonald: Avivo Biomedical Inc.
Jayachandran N. Kizhakkedathu: University of British Columbia
Stephen G. Withers: University of British Columbia
Michael L. Nicholson: University of Cambridge

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-47131-9

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