Subproject 1 - Ex vivo Organ Modification

Instead, immunological blindness has to be purchased by a general, usually lifelong, immunosuppression, which, despite all the progress made in biomarkers, immunosuppressive drugs and monitoring, still places a high burden on the patient. Our vision is a completely new approach to solving the problem of organ rejection: instead of inducing immunological blindness in the organ recipient, an immunological invisibility of the donor organ will be created – for a life without rejection and immunosuppression, better graft survival, better quality of life and more available organs.

The concept of tissue marker deactivation is based on a genetic modification of the organs by viral transduction during ex vivo perfusion in an organ preservation system. The cells are genetically modified in such a way that the MHC genes can no longer be expressed as proteins on the cell surface. The elimination of these target structures of immunological rejection at the donor-recipient interface leads to immunological invisibility of the modified cells to the recipient's immune system. An immunological recognition as foreign is thus no longer possible despite a fully functional immune system of the recipient. In previous investigations with cells and tissues, rejection could be completely prevented in this way without the need for immunosuppression. 

This project investigates ex vivo organ modification and transplantation of optimized organs in a preclinical kidney transplant model. The methods of ex vivo transduction will be developed and the optimal conditions for organ perfusion will be determined in cooperation with IKME/HsH. Once protocols have been established, modified kidneys are transplanted into allogeneic recipient pigs and rejection monitoring is performed. If the process is successful, the clinical study is prepared.