B1: Multi-transgenic pigs as universal donors for pig-to-primate xenotransplantation”

The goal of this project is to provide the consortium with advanced (multi-transgenic) porcine xenografts, including heart valves, solid organs and cells compatible with long term survival after pig-to-primate xenotransplantation. We will reach these goals by refining our multi-transgenic pig approach (Gal Ko/CMAH-ko/CD49/CD55/CD59/hHo-1/hA20), by creating and characterizing pigs with down-regulation of MHC epitopes, by producing porcine cells with expression of Indolamin-2,3-Dioxygenase (IDO) and by knocking out PERV loci in the porcine genome using CRISPR/Cas. The biological significance of the genetic modifications will be tested in vitro and in an ex vivo perfusion system prior to providing organs for solid organ transplantation. Thus, the project plays a major role for nearly all members of the TR-SFB consortium.