Human decay accelerating factor transgenic pigs for xenotransplantation obtained by sperm-mediated gene transfer

Abstract

UMAN organs for transplantation are insufficient in quantity, and for every organ transplant undertaken there is a need for an additional five to ten organs. Waiting lists are constantly growing and many patients die before an organ can be found. Researchers continue to experiment with alternatives. One of these is xenotransplantation, which uses animals as donors and which presents an entirely new set of challenges. The pig is presently considered the most likely source of organs for human xenotransplantation because it is easy to breed, has compatibly sized organs, and offers the possibility of genetic manipulation. However, organ transplantation between distantly related species, such as pigs and humans, results in hyperacute rejection (HAR), involving the complement system. It may be possible to avoid rejection reactions by genetically engineering donor animals, so that the recipient’s immune system does not act on the graft. Thus, a number of research teams, including our group, have embarked on programs to produce pigs transgenic for the human regulators of complement activation (RCAs) genes, in the attempt to produce pigs whose organs may be suitable for transplantation into humans. 1‐3 The present study reports on the production of pigs transgenic for the human regulator of complement activation human decay accelerating factor (hDAF) by spermmediated gene transfer (SMGT), a highly efficient and reproducible alternative to microinjection, presently the most widely used system for generating transgenic animals.