|[Frontiers in Bioscience, 2, e1-11, April 1, 1997]|
TRANSGENIC APPROACHES FOR THE REDUCTION IN EXPRESSION OF GALalpha(1,3)GAL FOR XENOTRANSPLANTATION|
Mauro S. Sandrin, Narin Osman, Ian F.C. McKenzie
Molecular Immunogenetics Laboratory, Austin Research Institute, Austin & Repatriation Medical Center, Heidelberg Vic. 3084, Australia
Received 12/31/96; Accepted 3/12/97; On-line 4/1/97
A solution to the world-wide problem of transplant organ supply and demand that is gaining increasing attention is the use of xenogeneic organs ie. tissues obtained from animal species other than humans. Based on physiological, biological and ethical considerations, the pig would appear to be the most suitable donor for xenotransplantation (1, 2). However, there is a major problem in that all humans have large amounts of natural antibodies to pig tissues that could bind to Galalpha(1,3)Gal found in all pig tissues, activate complement and cause hyperacute rejection of transplanted organs. Pigs and humans last shared a common ancestor 64 million years ago, and there are many antigenic differences of importance in the pig-to-human immune response. However, with respect to hyperacute rejection the majority, if not all of the natural antibody is directed to a single carbohydrate epitope Galalpha(1,3)Gal (3-5).