Current status and perspectives for the generation of transgenic pigs for xenotransplantation

Xenotransplantation implies transplantation of organs between discordant, e.g. non-related species. This procedure usually is associated with a hyperacute rejection response (HAR) which destroys the transplanted organ within minutes. To overcome the growing shortage of human organs, transgenic pigs have been generated that express human complement regulatory genes. This approach enables to overcome the HAR as shown by an extended average survival rate of 40-90 days of the immunosuppressed primate recipient of a transgenic porcine heart. It is expected that transgenic pigs will be available as organ donors within the next 5-7 years. A major prerequisite is the prevention of the potential transfer of pathogenic microorganisms, in particular porcine endogenous retroviruses (PERV). Transgenic livestock has been generated predominantly via microinjection of DNA-constructs into pronuclei of zygotes. However, efficiency is low and only 1-3% transgenic offspring are to be obtained. Integration of the transgene occurs at random and expression is independent from the number of integrated copies but can be affected by the integration site. Improvements of the efficiency in the generation of transgenic pigs will be achieved by the use of genetically modified donor cells in nuclear transfer technology (cloning).