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AssigneeGeron Corporation
InventorsChris Denning, A. John Clark, J. Michael Schiff
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This disclosure provides a system for generating animal tissue with carbohydrate antigens that are compatible for transplantation into human patients. The tissue is inactivated homozygously for expression of α(1,3)galactosyltransferase, and comprises a transgene for α(1,2)fucosyltransferase. As a result, cell-surface N-acetyl lactosamine is not converted to the Galα(1,3)Gal xenoantigen. Instead, it is converted to Fucα(1,2)Gal, which is H substance, a self-antigen in humans. The tissue may also contain A or B-transferase, which will cause H substance to be converted into other ABO blood group antigens for compatibility with patients of the same blood type. This invention improves transplant compatibility of the xenograft tissue by lessening the risk of reactions resulting from xenoantigen and unconverted N-acetyl lactosamine acceptor determinants.
A transgenic pig whose genome comprises a homozygous inactivation of the α1,3GT gene, and wherein said genome further comprises a DNA sequence encoding α1,2FT, operably linked to a promoter and expressed wherein cells, tissue, or organs of said pig exhibit reduced hyperacute rejection.
An isolated porcine cell whose genome comprises a homozygous inactivation of the α1,3GT gene, and wherein said genome further comprises a DNA sequence encoding α1,2FT, operably linked to a promoter and expressed wherein said cell exhibits reduced hyperacute rejection.
Isolated porcine tissue comprising a porcine cell whose genome comprises a homozygous inactivation of the α1,3GT gene, and wherein said genome further comprises a DNA sequence encoding α1,2FT, operably linked to a promoter and expressed wherein said tissue exhibits reduced hyperacute rejection.
Dependencies are inferred from the claim text.