Persistent severe shortages of human donor organs for transplantation have resulted in great interest in the use of the pig as an organ donor. Hyperacute rejection of pig organs, mediated by preformed primate antibodies against alpha-1,3-galactosyl epitopes, is a barrier that must be overcome for eventual use of pigs as organ donors for human transplants. Elimination of 1,3- galactosyl epitopes from pig cells is an innovative and necessary approach to the problem of hyperacute rejection, as other approaches have proven insufficient to eliminate critical organ damage or to have only transient effectiveness. BioTransplant proposes to produce pigs, for use in solid organ xenotransplantation, that are totally deficient in the expression of alpha-1,3- galactosyl epitopes. This will be accomplished through use of nuclear transfer technologies with donor karyoplasts carrying a genetic knockout of the alpha- 1,3-galactosyltransferase (galtransferase) locus. Development of nuclear transfer in pigs is necessitated by the lack of alternative methods for production of transgenic large animals with gene-targeted alterations. PROPOSED COMMERCIAL APPLICATIONS: Organ transplantation is an established therapy for end-stage organ disease. However, there is a critical worldwide shortage of organs and increasingly large waiting lists have been established for potential organ transplant recipients. Recent statistics indicate that more than 60,000 people with end stage organ disease in the United States alone await organ transplants and that about 4,000 people die annually while waiting. Xenotransplantation is the only likely long-term solution to the chronic shortage of donor organs.
