Combined transgenic expression of α-galactosidase and α1,2-fucosyltransferase leads to optimal reduction in the major xenoepitope Galα(1,3)Gal

• DOI: 10.1073/pnas.94.26.14677
• Publication Date: 2002-07-26T14:32:33Z
• Authors: Narin Osman; Ian F. C. McKenzie; Karen Ostenried; Yiannis A. Ioannou; Robert J. Desnick; Mauro S. Sandrin
• Keywords: Fucosyltransferase; Fucosylation

Hyperacute rejection of pig organs by humans involves the interaction Galα(1,3)Gal with antibodies and complement. Strategies to reduce amount xenoantigen were investigated overexpression human lysosomal α-galactosidase in cultured porcine cells transgenic mice. The endothelial COS resulted a 30-fold reduction cell surface 10-fold reactivity natural antibodies. Splenocytes from mice overexpressing showed only 15–25% binding anti-Galα(1,3)Gal antibodies; however, this decrease was functionally significant as demonstrated reduced susceptibility antibody-mediated lysis. However, because there is residual degalactosylation results exposure N -acetyllactosamine residues potential new xenoepitopes, using alone unlikely overcome hyperacute rejection. We previously reported that α1,2-fucosyltransferase transgene had ≈90% levels due masking fucosylation; we evaluated effect on levels. Galα(1,3)Gal-positive expressing α1,3-galactosyltransferase, α1,2-fucosyltransferase, negligible staining not susceptible lysis serum containing antibody Thus, effectively expression could be used produce pigs Galα(1,3)Gal, thereby having no improving graft survival.