Multicellular living organisms and unmodified parts thereof and – Nonhuman animal – Transgenic nonhuman animal
Patent
1996-07-03
2000-12-26
Chambers, Jasemine C.
Multicellular living organisms and unmodified parts thereof and
Nonhuman animal
Transgenic nonhuman animal
800 21, 800 22, 800 25, 800 3, A01K 6700
Patent
active
061662887
ABSTRACT:
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.
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Byrne Geurard W.
Diamond Lisa E.
Logan John S.
Sharma Ajay
Chambers Jasemine C.
Clark Deborah J. R.
Cooper Iver P.
Guthrie Janice
Nextran Inc.
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