Expression of the human α:1,2‐fucosyltransferase in transgenic pigs modifies the cell surface carbohydrate phenotype and confers resistance to human serum‐mediated cytolysis

• DOI: 10.1096/fasebj.13.13.1762
• Publication Date: 2018-01-25T09:42:55Z
• Authors: Cristina Costa; Lisa Zhao; Willis V. Burton; Kenneth R Bondioli; Barry L. Williams; Thomas A. Hoagland; Paul A. Ditullio; Karl M. Ebert; William L. Fodor
• Keywords: Fucosyltransferase; Xenotransplantation

Hyperacute rejection (HAR) is the first critical immunological hurdle that must be addressed in order to develop xenogeneic organs for human transplantation. In area of cell-based xenotransplant therapies, natural antibodies (XNA) and complement have also been considered barriers successful engraftment. Transgenic expression inhibitors donor cells has significantly prolonged survival xenografts. However, without eliminating antibody reactivity may provide insufficient protection clinical application. An approach designed prevent XNA during HAR alpha1, 2-fucosyltransferase (H-transferase, HT). H-transferase modifies cell surface carbohydrate phenotype cell, resulting universal O antigen a concomitant reduction antigenic Galalpha1,3-Gal epitope. We engineered various transgenic pig lines express HT different tissues, including vascular endothelium. demonstrate two containing promoter constructs, can differentially regulated constitutive cytokine-inducible manner. The results significant epitope, reduced reactivity, an increased resistance serum-mediated cytolysis. pigs promise become key components development