SECOND GENERATION ADENOVIRUS AND VASCULAR GENE TRANSFER

第二代腺病毒和血管基因转移

• 批准号: 2031318
• 负责人: SAMUEL E GEORGE
• 金额: $ 19.13万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-04-10 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2031318
• 关键词: Adenoviridae; atherosclerosis; cholesterol; dietary lipid; disease /disorder model; gene therapy; laboratory rabbit; nitric oxide; nonhuman therapy evaluation; nutrition related tag; pathologic process; superoxide dismutase; transfection; transfection /expression vector; vascular endothelium; vasculitis

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.

描述：（从应用程序改编）基因转移技术是 在对基因疗法的激烈评估下，但其真正的承诺可能是 用于研究血管的分子和细胞机制的工具 疾病。 使用腺病毒载体转移基因转移已成功 在血管气球受伤后治疗新内膜增生，但 载体本身会诱导大量的炎症和细胞增殖。 幸运的是，第二代腺病毒载体大大降低了 病毒复制和结构基因表达，因此可能 代表几乎惰性基因转移载体。 因此，PI将 研究这些较新向量对血管基因转移的影响， 确定它们对急性和慢性炎症的影响及其能力 实现长期血管转基因表达。 随后，他会的 使用此矢量研究起源和随后的影响 内皮功能障碍是最早的阶段 胆固醇喂养的兔子中的动脉粥样硬化过程。 具体来说，他会的 确定腺病毒转移是否旨在增强血管 一氧化氮或减少超氧化物会有利地影响动脉粥样硬化 过程。 拟议的研究将确定 第二代腺病毒载体在第一代载体上有所改善， 并将定义仍然存在的问题的程度。 另外， 拟议的研究将使用腺病毒基因转移作为增强的工具 了解动脉粥样硬化的早期阶段。 成就 这些目标将有助于我们对动脉粥样硬化的理解 动脉粥样硬化，并增加血管基因疗法的可能性 被证明是治疗人动脉粥样硬化的有效选择。