학술논문

Enzymatic conversion of human blood group A kidneys to universal blood group O
Document Type
article
Source
Nature Communications, Vol 15, Iss 1, Pp 1-14 (2024)
Subject
Science
Language
English
ISSN
2041-1723
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.