SECOND GENERATION ADENOVIRUS AND VASCULAR GENE TRANSFER

描述：(改编自应用程序)基因转移技术是 正在对基因疗法进行激烈的评估，但它真正的希望可能是作为一种 研究血管分子和细胞机制的工具 疾病。用腺病毒载体进行基因转移在 治疗血管球囊损伤后的新生内膜增殖，但 载体本身会导致大量炎症和细胞增殖。 幸运的是，第二代腺病毒载体已经大大减少了 病毒复制和结构基因表达，因此可能 代表近乎惰性的基因转移载体。因此，PI将 研究这些新载体对血管基因转移的影响， 测定它们对急性和慢性炎症的作用及其能力 以影响长期的血管转基因表达。随后，他将 使用此向量来调查 血管内皮细胞功能障碍出现在血管病变早期阶段 胆固醇喂养兔的动脉粥样硬化形成过程。具体来说，他将 确定腺病毒转移旨在增强血管功能的基因 一氧化氮或还原超氧化物均有利于动脉粥样硬化的发生 进程。拟议的研究将在多大程度上确定 第二代腺病毒载体在第一代载体的基础上改进， 并将确定仍然存在的问题的程度。此外， 拟议的研究将使用腺病毒基因转移作为一种工具来增强 对动脉粥样硬化早期阶段的认识。取得的成就 这些目标将有助于我们理解动脉粥样硬化。 动脉粥样硬化，并增加血管基因治疗将 已被证明是治疗人类动脉粥样硬化的有效选择。

DESCRIPTION: (Adapted from the application) Gene transfer technology is under intense evaluation for gene therapy, but its real promise may be as a tool for investigating the molecular and cellular mechanisms of vascular disease. Gene transfer using adenoviral vectors has been successful in treating neointimal proliferation following vascular balloon injury, but the vector itself induces substantial inflammation and cellular proliferation. Fortunately, second generation adenoviral vectors have substantially reduced viral replication and structural gene expression, and therefore, may represent nearly inert gene transfer vectors. Accordingly, the PI will study the effect of these newer vectors on vascular gene transfer, determining their effect on acute and chronic inflammation and their ability to effect long-term vascular transgene expression. Subsequently, he will use this vector to investigate the origin and subsequent effects of endothelial dysfunction that is present in the earliest phases of the atherogenic process in cholesterol-fed rabbits. Specifically, he will determine whether adenoviral transfer of genes designed to enhance vascular nitric oxide or reduce superoxide will favorably affect the atherosclerotic process. The proposed studies will establish the degree to which second-generation adenoviral vectors improve upon first-generation vectors, and will define the extent of problems that remain. In addition, the proposed studies will use adenoviral gene transfer as a tool to enhance understanding of the early phases of atherosclerosis. The achievement of these goals will contribute to our understanding of atherosclerosis atherogenesis, and increase the likelihood that vascular gene therapy will prove to be an effective option for treatment of human atherosclerosis.