Nanoparticle Analysis of Enveloped Virus Entry Pathways

包膜病毒进入途径的纳米颗粒分析

基本信息

批准号：
7856237
负责人：
ROBERT A DAVEY
金额：
$ 12.35万
依托单位：
UNIVERSITY OF TEXAS MED BR GALVESTON
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-05-01 至 2011-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7856237
关键词：
Address Adopted Adsorption Adverse effects Affect Affinity Aftercare Antibodies Antiviral Agents Arts Attention Binding Biochemical Biological Assay Caliber Capsid Categories Caveolins Cell membrane Cells Chemistry Clathrin Confocal Microscopy Cryoelectron Microscopy Cytoplasm Cytosol Development Diagnostic Dominant-Negative Mutation Drug Formulations Endoplasmic Reticulum Environment Enzymes Evolution Friend Murine Leukemia Virus Genes Goals Golgi Apparatus Human Immune response Incubated Infection Kinetics Label Life Ligands Lipids Membrane Membrane Fusion Methods Murine leukemia virus Nanotechnology Neutralization Tests Organelles Parents Pathway interactions Penetration Peptides Pharmaceutical Preparations Pharmacotherapy Property Proteins Receptor Cell Role Site Specificity Supporting Cell Surface System Techniques Technology Testing Therapeutic Agents Tissues United States National Institutes of Health Vaccine Design Vaccines Venezuelan Equine Encephalitis Virus Virion Virus Virus Diseases Work cell type design dosage drug development drug efficacy env Gene Products immunogenicity improved nanoparticle nanoscale novel particle premature receptor trafficking uptake virus envelope wasting

Address Adopted Adsorption Adverse effects Affect Affinity Aftercare Antibodies Antiviral Agents Arts Attention Binding Biochemical Biological Assay Caliber Capsid Categories Caveolins Cell membrane Cells Chemistry Clathrin Confocal Microscopy Cryoelectron Microscopy Cytoplasm Cytosol Development Diagnostic Dominant-Negative Mutation Drug Formulations Endoplasmic Reticulum Environment Enzymes Evolution Friend Murine Leukemia Virus Genes Goals Golgi Apparatus Human Immune response Incubated Infection Kinetics Label Life Ligands Lipids Membrane Membrane Fusion Methods Murine leukemia virus Nanotechnology Neutralization Tests Organelles Parents Pathway interactions Penetration Peptides Pharmaceutical Preparations Pharmacotherapy Property Proteins Receptor Cell Role Site Specificity Supporting Cell Surface System Techniques Technology Testing Therapeutic Agents Tissues United States National Institutes of Health Vaccine Design Vaccines Venezuelan Equine Encephalitis Virus Virion Virus Virus Diseases Work cell type design dosage drug development drug efficacy env Gene Products immunogenicity improved nanoparticle nanoscale novel particle premature receptor trafficking uptake virus envelope wasting

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项目摘要

DESCRIPTION (provided by applicant): In the field of nanotechnology, much attention has been paid to the construction of nanometer- sized particles that can harbor drugs and other therapeutic agents. However, beyond the use of static ligands such as antibodies and small peptides, little work has been done on the specific targeting of the nanoparticles (NPs). This is an important component of NP design. By selectively delivering drugs to one cell over another, the efficacy of the drug can be drastically improved and consequently reduce the dosage needed and potential side effects. Viruses share many structural and physical similarities to an idealized NP. They are both about 100 nm in diameter, have hydrophilic shells and have long circulatory lives. However, viruses achieve a feat that few NP designs can; they efficiently target specific tissues and cells using virus envelope proteins (envs). The envs also do something that designed ligands may never achieve; they target specific cellular endocytic pathways, to access organelles such as the Golgi and the endoplasmic reticulum. Envs are also simple membrane fusion engines that sense the surrounding environment to trigger the release of their cargo in the cell cytoplasm at specific sites. In this proposal, we will optimize techniques to construct fluorescent NPs coated in the envs of Friend murine leukemia virus, Venezuelan equine encephalitis virus (NIH category B agent) and Ebola (NIH category An agent). Each env targets virus to unique cell receptors and endocytic entry pathways. We will investigate the cell and organelle targeting properties of the coated envs using state-of-the-art confocal microscopy and biochemical methods. Together with a novel way to target NPs, this work will allow a better understanding of the role of envs in infection and the entry pathways used by each virus. This will identify new targets for antiviral drug development. The NPs will also be useful in rapid virus diagnostic assays. Project Narrative: Highly purified virus membranes will be used to coat nanoparticles using a new method that preserves the useful features of the virus envelope proteins. The nanoparticles will then be tested for their ability to specifically interact with and enter cells. This will greatly aid in the development of targeted drug therapies and vaccine design.

描述（由申请人提供）：在纳米技术领域，已经非常关注纳米尺寸的颗粒，这些纳米尺寸的颗粒可以藏有药物和其他治疗剂。但是，除了使用静态配体（例如抗体和小肽）之外，对纳米颗粒（NP）的特定靶向量很少进行。这是NP设计的重要组成部分。通过选择性地将药物递送到另一个细胞上，可以大大改善该药物的功效，从而减少所需的剂量和潜在的副作用。病毒与理想化的NP具有许多结构和物理相似性。它们的直径约为100 nm，具有亲水性壳，并且具有较长的循环寿命。但是，病毒实现了很少有NP设计的壮举。它们使用病毒包膜蛋白（ENKS）有效地靶向特定的组织和细胞。 Envs还做一些设计配体可能永远无法实现的事情。它们靶向特定的细胞内吞途径，以进入诸如高尔基体和内质网等细胞器。 Envs也是简单的膜融合发动机，它感知周围环境在特定部位触发其货物在细胞质中的释放。在此提案中，我们将优化在朋友鼠白血病病毒，委内瑞拉卑鄙的脑炎病毒（NIH B类代理商）和埃博拉病毒（NIH类药物A类）中构造覆盖的荧光NP的技术。每个ENV都将病毒靶向独特的细胞受体和内吞进度途径。我们将使用最先进的共聚焦显微镜和生化方法研究涂层ENV的细胞和细胞器靶向性能。这项工作将与一种针对NP的新颖方法一起，可以更好地理解ENV在感染中的作用以及每种病毒使用的进入途径。这将确定抗病毒药物开发的新靶标。 NP也将在快速病毒诊断测定中有用。项目叙述：高度纯化的病毒膜将使用一种保留病毒包膜蛋白有用特征的新方法来覆盖纳米颗粒。然后，将测试纳米颗粒的特殊交互和进入细胞的能力。这将极大地帮助开发目标药物疗法和疫苗设计。