Abstract: One of the problems facing transplantation procedures today is the availability of organs suitable for transplantation. A way around the lack of organs, it to harvest organs from animals. However, immune reactions between discordant donor and recipient mammals presents a major obstacle in such transplantation procedures. The production of transgenic non-human mammals expressing a DNA sequence encoding an homologous complement restriction factor or factors of a discordant mammalian species such that the expression of the DNA sequence would prevent xenograft rejection by the host mammal's immune system would provide organs, tissues and cells for transplantation.

Abstract: Conventionally, animal tissue from one species can only be transplanted into another species when the species are concordant; otherwise, hyperimmune rejection ensues. In this invention, donor tissue is modified, for example by being transgenic, to express or otherwise be in association with one or more substances, referred to as homologous complement restriction factors (HCRFs), which are active in the recipient species to prevent the complete activation of complement and therefore rejection. The invention is in part based on the discovery that the alternative pathway of complement activation, rather than the classical pathway, is responsible for hyperacute discordant xenograft rejection.