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AssigneeNextran Inc.
InventorsLisa E. Diamond, John S. Logan, Geurard W. Byrne, Ajay Sharma
Estimating the term…
A method of xenotransplanting organs, tissues, cells or non-viable components which reduces or prevents antibody-mediated rejections, including hyperacute rejection, is provided wherein transgenic animals are produced that express at least one enzyme which masks or reduces the level of the antigenic Gal.alpha.(1,3)Gal or gal epitope, and at least one complement inhibitor such as CD59, DAF and/or MCP. The transgenic animals which express both a gal epitope-reducing enzyme and a complement inhibitor will have masked or reduced levels of the gal epitope and will be much less likely to produce an antibody-mediated rejection following transplantation, and the expression of the complement inhibitor will also suppress complement activation and reduce even further a severe immune reaction following the transplantation of donor organs, tissue, cells or non-viable components from the transgenic animals so produced. In addition, transgenic animals are provided which express a plurality of complement inhibitors or other proteins from a locus of genes at a single integration site. The present invention is thus advantageous in that it can provide xenogeneic organs, tissues, cells and non-viable components which can be transplanted safely and effectively into humans with a reduction or elimination of antibody-mediated rejection to an extent not previously possible, and which will significantly reduce the need to obtain donor organs, tissues, cells or non-viable components from human or primate donors.
A method of preparing organs, tissues, or cells for xenotransplantation into human patients with reduced rejection comprising the steps of:
A nonhuman transgenic animal useful for providing organs, tissues, or cells for use in xenotransplantation, which is able to stably express (a) at least one transgenically encoded enzyme functional in said animal which masks or reduces the level of a zenoreactive antigen, said enzyme being a fucosyltransferase, and (b) at least one transgenically encoded complement inhibitor functional in humans, said animal being a source of transplant material, in the form of an organ, tissue, or cell, which is anatomically and physiologically compatible with a human recipient, wherein the likelihood or severity of hyperacute rejection of said material, as a result of transplantation of said material into a human patient, is reduced relative to the likelihood or severity of such rejection of said material in the absence of said expresssion, and wherein said animal is a pig.
A method of producing nonhuman transgenic animals useful in xenotransplantation with reduced rejection comprising introducing into said animal a nucleic acid that expresses at least one enzyme functional in said animal which masks or reduces the level of a zenoreactive antigen, said enzyme being a fucosyltransferase, and nucleic acid that expresses at least one complement inhibitor functional in humans, said animal being a source of an organ, tissue, or cell for xenotransplantation into humans, and anatomically and physiologically compatible with a human patient said animal being a pig.
Dependencies are inferred from the claim text.