Abstract: The present invention relates to methods and compositions for the reduction of xenotransplantation rejection. Specifically, the present invention relates, first, to transgenic cells, tissues, organs and animals containing transgenic nucleic acid molecules that direct the expression of gene products, including, but not limited to enzymes, capable of modifying, either directly or indirectly, cell surface carbohydrate epitopes such that the carbohydrate epitopes are no longer recognized by natural human antibodies or by the human cell-mediated immune response, thereby reducing the human immune system response elicited by the presence of such carbohydrate epitopes. In a preferred embodiment, the transgenic cells, tissues, organs and animals express nucleic acid molecules encoding functional recombinant &agr;-Galactosidase A (&agr;GalA) enzyme which modifies the carbohydrate epitope Gal&agr;(1,3)Gal.

Abstract: DNA sequences encoding a porcine Gal.alpha.(1,3) galactosyl transferase and clones containing such sequences are provided. The porcine Gal.alpha.(1,3) galactosyl transferase produces the Gal.alpha.(1,3)Gal epitope on the surfaces of porcine cells. This epitope is recognized by human anti-Gal.alpha.(1,3)Gal antibodies which are responsible for hyperacute rejection of xenotransplanted pig cells, tissues and organs.