Viral strategies for xenotransplantation

• Applicant: Professor Dr. Christian Kupatt
• Subject Area: Cardiac and Vascular Surgery
• Term: from 2007 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5470814

The critical shortage of human donor organs has generated growing interest for porcine to human xenotransplantation. In order to overcome the major immunological barriers to xenotransplantation, genetic strategies have to be developed that ensure long-term engraftment of the organ. To this end, immune-modulatory transgenes have to be efficiently expressed. Viral vectors are powerful tools for expression of foreign genes, in particular in explanted and isolated organs as well as in mesenchymal stem cells ex vivo. Using vectors derived from adeno-associated virus (AAV) and lentiviral vectors, we will transduce donor organs with immune-modulatory transgenes to develop novel strategies to overcome xenotransplant rejection. Using lentiviral gene transfer, gain-of-function cell lines can be generated with high efficacies in pig mesenchymal stem cells, which will subsequently be applied to allo- and xenotransplants and regulate the immune response. A major goal of this project is to apply viral organ- or cell-transduction to multitransgenic pigs for xenotransplantation.

• DFG Programme: Research Units
• Subproject of: FOR 535: Xenotransplantation
• Participating Persons: Professor Dr. Alexander Pfeifer; Professor Dr. Michael Schmoeckel