Xenografts are an achievable breakthrough

The objective of this communication is to show that pig-to-human organ transplantation could be feasible through genetic engineering. By introducing into donor pigs several different tolerance promoting genetic modifications there can be a synergistic effect to produce extended tolerance for xenografted organs in human recipients. Nuclear-transfer cloning allows production of pigs with knockout mutations in the galactose-alpha-1,3-galactosyl transferase gene, in principle eliminating hyperacute rejection. Once hyperacute rejection is circumvented, long-term tolerance of xenografted organs should be possible through a combination of transgenic immunomodulating molecule, bone marrow chimerism and short to intermediate term use of immunosuppressive drugs. If immunomodulating transgenes; are deleterious during pig development, inducible cre-recombinase excision of stop codons provides a means to delay expression of such transgenes until after transplantation. Zoonotic diseases can be circumvented via pathogen-free colonies and additional knockout mutations to disable porcine endogenous retrovirus and prion disease. Thus, there is now a technical and theoretical framework for serious efforts at cross-species transplantation. (C) 2004 Elsevier Ltd. ALL rights reserved.