MOLECULAR AND CELLULAR TRANSPORT IN MUCUS

粘液中的分子和细胞运输

• 批准号: 8172722
• 负责人: W. Mark Saltzman
• 金额: $ 4.8万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172722
• 关键词: Acquired Immunodeficiency Syndrome; Animals; Antibodies; Antiviral Therapy; Asians; Blood; Cells; Cellular Tropism; Chronic Disease; Computer Retrieval of Information on Scientific Projects Database; Disease Progression; Euthanasia; Event; Funding; Glycolates; Goals; Grant; HIV Infections; HIV-1; Human; Immune response; Individual; Infection; Institution; Knowledge; Laboratories; Local Microbicides; Macaca; Macaca mulatta; Modeling; Molecular; Mucous body substance; Nature; Pattern; Polymers; Research; Research Personnel; Resources; Route; SIV; Sampling; Schedule; Small Interfering RNA; Source; Time; Tissues; United States National Institutes of Health; Vaccines; Viral; Viral Load result; Virus; design; in vivo; lymph nodes; mucosal site; nanoparticle; particle; transmission process

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Currently, more than 40 Million people worldwide are persistently infected with HIV-1. Similar to HIV infection in humans, SIV infection in Asian macaques results in chronic disease that culminates in AIDS. The well-defined SIV infection of rhesus macaques closely resembles many aspects of HIV infection in humans including events associated with transmission, cellular tropism of the virus, viral replication patterns, disease progression, and the nature of the host immune response. Furthermore, the SIV/macaque model is important because knowledge of the time, route, and number of viral exposures is known, the viral stock used to infect the macaques is well-characterized, and there is the ability to frequently sample important tissues (blood, lymph nodes, mucosal sites, etc) throughout infection. One of the current main lines of research in the field of AIDS is the identification of new treatments that will result in reduction or suppression of viral loads in infected individuals. The goal of this project is to determine the in vivo efficacy of biodegradable poly (lactic-co-glycolic acid) polymers (PLGA) nanoparticles that carry small interfering RNAs (siRNAs) specific for SIVmac. In order to target mainly infected cells, the particles will also be coated with anti-CD4 antibodies. This study will use rhesus macaques already infected with SIV. The animals proposed for the first year of the project are already available from other studies performed by our laboratory. For subsequent years we propose to use animals from other AIDS projects at SNPRC (such as vaccine projects) that become infected with SIV and are scheduled for euthanasia. Thus, we will not increase the use of na¿ve animals; rather, we will increase the scientific value of animals that otherwise would be scheduled for euthanasia. If the results of these studies are successful, these biodegradable nanoparticles could be used in humans as an addition to traditional antiviral therapy, or for the design of topical microbicides.

该副本是使用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这是调查员的机构。 目前，全世界有超过4000万人持续感染HIV-1。与人类的艾滋病毒感染相似，亚洲猕猴的SIV感染导致慢性疾病最终导致艾滋病。恒河猕猴的SIV感染明确，与人类中HIV感染的许多方面相似，包括与传播相关的事件，病毒的细胞向性，病毒复制模式，疾病进展以及宿主免疫反应的性质。此外，SIV/猕猴模型很重要，因为知道了病毒暴露的时间，路线和数量，用于感染猕猴的病毒量很高，并且在整个感染过程中都有经常采样重要的时间（血液，淋巴结，粘膜等）的能力。 艾滋病领域的当前研究主要研究线之一是鉴定新的治疗方法，这些治疗方法将减少或抑制感染者的病毒负荷。该项目的目的是确定可生物降解的聚（乳酸 - 乙醇酸）聚合物（PLGA）纳米颗粒的体内效率，这些纳米颗粒具有小型干扰RNA（siRNA）对SIVMAC。为了靶向主要被感染的细胞，颗粒也将用抗CD4抗体涂覆。这项研究将使用已经感染SIV的恒河猕猴。该项目第一年提出的动物已经可以从我们的实验室进行的其他研究中获得。随后的几年，我们建议使用SNPRC（例如疫苗项目）的其他AIDS项目的动物，这些动物感染了SIV，并计划用于安乐死。那就是我们不会增加动物的使用；相反，我们将提高动物的科学价值，否则将安排安乐死。 如果这些研究的结果成功，这些可生物降解的纳米颗粒可以在人类中用作传统抗病毒疗法的补充，或设计局部杀菌剂的设计。