NEW METHODOLOGY FOR VEGF MEDIATED GENE DELIVERY

这个项目的总体目标是开发一种商业上可行的 选择性基因输送给生长中的内皮细胞的系统。生长 血管生成几乎发生在内皮细胞的基础上 在病态情况下独家使用，并由 内皮细胞特异性细胞因子血管内皮生长因子 (血管内皮生长因子)。 在第一阶段，我们建议开发一种新的方法，用于血管内皮生长因子介导的 基因传递，消除了对生长的直接化学处理 因子或DNA，并显著增加每个血管内皮生长因子的DNA负载量 分子。 在第二阶段的研究中，我们会达致以下目标： 选择性影响生长中的内皮细胞的基因，测试血管内皮生长因子 在动物模型中用于基因传递的融合蛋白，并开发一种 用于基因治疗的商业可行的血管内皮生长因子融合蛋白载体。 建议的商业应用： 作为这一项目的结果而开发的基因传递工具可能是 用于治疗几种主要的血管生成依赖的病理。 在本项目期间开发的方法可以扩展到其他 基于细胞因子的疗法。

The overall goal of this project is to develop a commercially viable system for selective gene delivery to growing endothelial cells. Growth of endothelial cells underlies angiogenesis that occurs almost exclusively in pathological situations and is promoted by the endothelial call specific cytokine vascular endothelial growth factor (VEGF). In Phase I we propose to develop a new methodology for VEGF-mediated gene delivery that eliminates direct chemical treatment of the growth factor or DNA, and dramatically increases the load of DNA per VEGF molecule. In Phase II studies we will pursue the following aims: selection of genes that selectively affect growing endothelial cells, testing VEGF fusion proteins for gene delivery in animal models, and developing a commercially viable VEGF fusion protein vehicle for gene therapy. PROPOSED COMMERCIAL APPLICATION: The gene delivery vehicle developed as a result of this project may be used for treatment of several major angiogenesis-dependent pathologies. The methodology developed during this project may be expanded to other cytokine-based therapeutics.