Viral strategies for xenotransplantation

人类供体器官的严重短缺引起了人们对猪与人类异种移植的兴趣。为了克服异种移植的主要免疫障碍，必须开发确保器官长期植入的遗传策略。为此，必须有效地表达免疫调节转基因。病毒载体是外源基因表达的有力工具，特别是在外植和分离器官以及离体间充质干细胞中。利用腺相关病毒（AAV）和慢病毒载体衍生的载体，我们将用免疫调节转基因转导供体器官，以开发克服异种移植排斥反应的新策略。利用慢病毒基因转移，可以在猪间充质干细胞中高效地产生功能获得细胞系，这些细胞系随后将应用于同种异种移植和调节免疫反应。该项目的一个主要目标是将病毒器官或细胞转导应用于多转基因猪的异种移植。

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.