Viral strategies for xenotransplantation

异种移植的病毒策略

• 批准号: 45441849
• 负责人: Professor Dr. Christian Kupatt
• 金额: --
• 依托单位: Institut für Pharmakologie und Toxikologie
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2007
• 资助国家: 德国
• 起止时间: 2006-12-31 至 2012-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/45441849?language=en
• 关键词: Viral; strategies; xenotransplantation

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.

人类供体器官的严重短缺引起了人们对猪到人异种移植的兴趣。为了克服异种移植的主要免疫学障碍，必须开发确保器官长期植入的遗传策略。为此，免疫调节转基因必须有效表达。病毒载体是表达外源基因的有力工具，特别是在分离的和分离的器官以及离体间充质干细胞中。利用来自腺相关病毒（AAV）和慢病毒载体的载体，我们将用免疫调节转基因来修饰供体器官，以开发克服异种移植排斥反应的新策略。使用慢病毒基因转移，可以在猪间充质干细胞中高效地产生功能获得性细胞系，其随后将应用于同种异体和异种移植并调节免疫应答。本计画的主要目的是将病毒的器官或细胞转导应用于多转基因猪的异种移植。