Viral strategies for xenotransplantation

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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.