Methods of Preparing Tissues for Xenotransplantation Using Alpha-galactosidases

摘要

This invention relates to novel α-galactosidases for the enzymatic removal of the immunodominant monosaccharides on blood products and tissues. Specifically this invention provides a novel family of α3 glycosidases, used for the enzymatic removal of type B antigens from blood group B and AB reactive blood products, and the Galili antigen from non-human animal tissues, thereby converting these to non-immunogenic cells and tissues suitable for transplantation.

主权项

1. A method of preparing one or more tissues or organs for xenotransplantation, comprising the steps of:
i. incubating the tissue or organ with a polypeptide having alpha-galactosidase activity, thereby cleaving immunodominant alpha-1,3-linked terminal galactose residues from the tissue or organ, and ii. isolating the tissue or organ from the polypeptide and the enzymatically-cleaved immunodominant galactose residues, thereby rendering the tissue or organ suitable for xenotransplantation, the polypeptide comprising a sequence, the sequence comprising residues 1-329 of SEQ ID NO: 8, followed by nine contiguous amino acids DD(P/A)(V/I)N(V/I)HGT (SEQ ID NO:10), followed by residues 339-467 of SEQ ID NO: 8, followed by twenty-one contiguous amino acids DXXXW(Y/F)E(S/T)GXXXD(L/V)(L/T)I(K/R)XNXF (SEQ ID NO:11), followed by residues 489-615 of SEQ ID NO: 8, and wherein the polypeptide has alpha-galactosidase activity.