Genetic engineering for xenotransplantation

Journal of Cardiac Surgery
M S SandrinI F McKenzie

Abstract

Xenotransplantation is being pursued vigorously to solve the shortage of allogeneic donor organs. Experimental studies of the major xenoantigen (Gal) and of complement regulation enable model xenografts to survive hyperacute rejection. When the Gal antigen is removed or reduced and complement activation is controlled, the major barriers to xenograft survival include unregulated coagulation within the graft and cellular reactions involving macrophages, neutrophils, natural killer (NK) cells, and T lymphocytes. Unlike allografts, where specific immune responses are the sole barrier to graft survival, molecular differences between xenograft and recipient that affect normal receptor-ligand interactions (largely active at the cell surface and which may not be immunogenic), are also involved in xenograft failure. Transgenic strategies provide the best options to control antigen expression, complement activation, and coagulation. Although the Gal antigen can be eliminated by gene knockout in mice, that outcome has only become a possibility in pigs due to the recent cloning of pigs after nuclear transfer. Instead, the use of transgenic glycosyl transferase enzymes and glycosidases, which generate alternative terminal carbohydrates on g...Continue Reading

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Citations

Aug 14, 2003·Molecular Immunology·Tom E Mollnes, Arnt E Fiane
Mar 23, 2006·Infection and Immunity·Nathan J WeyandMagdalene So
Apr 5, 2014·PloS One·Paolo MartiniGerolamo Lanfranchi
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Jun 1, 2005·Carbohydrate Research·Stacey BrittonMario A Monteiro
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Jul 22, 2005·Immunology and Cell Biology·Paula Ramsland
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