Zielgerichtete Transduktion aktivierter Endothelzellen mit adenoviralen Vektoren großer DNA-Kapazität und Expression von angiostatischen Faktoren und Matrix Metalloproteinase (MMP) Inhibitoren (Targeted transduction of activated endothelial cells with hig

点击翻译按钮获取中文摘要

In vivo gene transfer will likely become a very important tool to study genes and their products in physiological and pathological conditions. A recently developed third-generation adenoviral vector has favourable safety features, decreased toxicity and immunogenicity, transduces efficiently many replicating and non-replicating celltypes in vivo and in vitro, is produced to high titers and has the advantage of 36 kb capacity for foreign DNA, allowing gene transfer of multiple expression cassettes or the inclusion of large regulatory sequences. Within this program we plan to develop a technology that is based on these new adenoviral vectors and that ca be used for targeted gene transfer into specific cell types. This will be achieved by abolishing the natural adenoviral tropism and at the same time introducing new ligands into the viral capsid that confer new targeting specificities. For proof-of-principle experiments we will target the avß3 integrin that is known to be highly expressed on activated endothelial cells. In collaboration with other members of this program we plan to express several transgenes including a dominant-negative VEGF receptor (KDR/Flk-1) mutant and metalloproteinase inhibitors. Targeting specificities and efficacies will be tested in appropriate in vitro and in vivo models.