Significant downregulation of the major swine xenoantigen by N-acetylglucosaminyltransferase III gene transfection.

Introduction of the beta-D-mannoside beta-1,4-N-acetylglucosaminyltransferase III (GnT-III) gene into swine endothelial cells (SEC) reduced their susceptibility to normal human serum (NHS) in complement-mediated cell lysis and also suppressed the antigenicity to human natural antibodies as evidenced by flow cytometric analysis, as well as Griffonia simplicifolia 1 isolectin (1B4 lectin) binding to the Gal alpha1-3 Gal beta 1-4 GlcNAc-R (the alpha-galactosyl epitope). Western blot analysis indicated that proteins smaller than 66 kDa had diminished reactivity to NHS and 1B4 lectin. GnT-III, a key enzyme involved in branch formation of N-linked sugars, was found to downregulate the expression of xenoantigen, suggesting that this approach may be of value in clinical xenotransplantation in the future.