ENDOCYTIC TRAFFICKING OF ADENOVIRUS GENE THERAPY VECTORS

基因治疗的未来取决于我们发现 提供和表达外源DNA的有效手段。 战略 基因转移继续沿着沿着几条路线进行， 利用病毒进入的天然机制的病毒载体， 在真核细胞中建立。 几种病毒之一， 用于载体生产的模板是腺病毒（Ad），其是一种骑入 通过与细胞表面蛋白结合并作为血浆进入细胞 细胞膜通过一种称为内吞作用的过程组成性地恢复。 一旦 在细胞内，核内体的酸化诱导病毒裂解 包围它的膜，并逃逸到细胞质，使病毒进入 到细胞核。 从核内体逃逸对病毒存活至关重要。 博士利奥波德和他的同事假设， 从一种细胞类型到另一种细胞类型的内体特征影响了 细胞对感染的相对易感性。 他们计划对此进行调查 通过（1）描述Ad在几种不同细胞中的内吞作用 对Ad感染易感性不同的类型，（2）描述 内吞过程中的微妙操纵的广告内吞过程中， 单细胞类型，和（3）描述Ad载体变体的内吞作用 在单个细胞类型中。 从这些研究中，他们希望获得一个 了解存在于内吞细胞中的自然变异的广度， 途径，因为他们影响广告在感染过程中，并确定关键 分子水平上的参与者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.