Goals of the project

In this project, we propose the development of optimized xenograft organ donor pigs which carry genetic modifications after targeted integration to ensure that the donor pigs can be efficiently propagated by breeding without Mendelian segregation of the transgenes. Additional xenoprotective transgenes will be placed into the GGTA1 locus using an innovative gene stacking approach and functionally evaluated using our unique pipeline of in vitro and ex vivo tests. The proposed experiments will make an essential contribution to clinical translation of organ xenotransplantation.

This project combines animal genetics and biotechnology with immunology, in particular humoral and cellular innate immunity, but also direct T cell activation by EC. In addition, biomedical engineering tools like microfluidic techniques for 3D culture of EC under pulsatile flow will be used. Only this synergistic combination of disciplines and approaches will allow for the breakthrough, which will be the availability of stable breeding cohorts of pigs with multiple genetic modifications, ready to provide organs for in-depth preclinical testing in pig-to-NHP xenotransplantations