ENDOCYTIC TRAFFICKING OF ADENOVIRUS GENE THERAPY VECTORS

描述：基因治疗的未来取决于我们发现 传递和表达外源DNA的有效手段。战略以实现 基因转移继续沿着几个方向取得进展，包括使用 利用病毒进入和传播的自然机制的病毒载体 在真核细胞中的建立。几种病毒中的一种，提供 用于生产载体的模板是腺病毒(Ad)，一种搭载到 通过与细胞表面蛋白结合并以血浆的形式进入细胞 膜是通过一种称为内吞作用的过程结构性地被回收的。一次 在细胞内，内小体的酸化诱导病毒裂解 它周围的膜，并逃逸到细胞溶质，使病毒进入 到细胞的细胞核。逃离内体是病毒生存的关键。 利奥波德博士和他的同事们假设， 从一种细胞类型到另一种细胞类型的内体特性影响 CELL=S相对感染易感性。他们计划对此进行调查 通过(1)描述Ad在几个不同细胞中的内吞作用的可能性 对Ad感染易感性不同的类型，(2)描述 在细微的内吞过程中，Ad的内吞作用 单细胞类型，以及(3)描述Ad载体的变种的内吞作用 在单一细胞类型中。从这些研究中，他们希望获得一个 对胞内存在的自然变异的广度的理解 在感染过程中影响Ad的途径，并确定关键 分子水平上的玩家可以影响广告的结果 感染。

DESCRIPTION: The future of gene therapy depends on our ability to find efficient means of delivering and expressing exogenous DNA. Strategies for gene transfer continue to progress along several lines including the use of viral vectors that capitalize on natural mechanisms of viral entry and establishment in eukaryotic cells. One of several viruses that provides a template for vector production is adenovirus (Ad), a virus that rides into cells by binding to cell surface proteins and entering cells as the plasma membrane is constitutively retrieved by a process called endocytosis. Once inside the cell, acidification of endosomes induces the virus to lyse the membrane that surrounds it and escape to the cytosol giving the virus access to the cell's nucleus. Escape from endosomes is crucial to viral survival. Dr. Leopold and his colleagues hypothesize that variation in the characteristics of endosomes from one cell type to another impacts the cell=s relative susceptibility to infection. They plan to investigate this possibility by (1) describing endocytosis of Ad in several distinct cell types that differ in susceptibility to Ad infection, (2) describing endocytosis of Ad during subtle manipulations of the endocytic process in a single cell type, and (3) describing endocytosis of variants of Ad vectors in a single cell type. From these studies, they expect to gain an understanding of the breadth of natural variation that exists in endocytic pathways as they affect Ad during infection, and to determine the key players at the molecular level that can influence the outcome of an Ad infection.