MOLECULAR AND CELLULAR TRANSPORT IN MUCUS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 目前，全球有4000多万人持续感染艾滋病毒-1。与人类感染艾滋病毒类似，亚洲猕猴感染SIV会导致慢性病，最终导致艾滋病。猕猴的SIV感染与人类HIV感染的许多方面非常相似，包括与传播相关的事件、病毒的细胞趋向性、病毒复制模式、疾病进展和宿主免疫反应的性质。此外，SIV/猕猴模型很重要，因为已知病毒暴露的时间、路线和数量，感染猕猴所用的病毒库具有良好的特性，并且能够在感染过程中经常对重要组织(血液、淋巴结、粘膜部位等)进行采样。 目前艾滋病领域的研究主线之一是确定新的治疗方法，以减少或抑制感染者的病毒载量。该项目的目标是确定携带针对SIVmac的小干扰RNA(SiRNAs)的可生物降解聚(乳酸-乙醇酸共聚)聚合物(PLGA)纳米颗粒的体内疗效。为了主要针对受感染的细胞，这些颗粒还将被包裹上抗CD4抗体。这项研究将使用已经感染SIV的恒河猴。该项目第一年提出的动物已经可以从我们实验室进行的其他研究中获得。在接下来的几年里，我们建议使用SNPRC其他艾滋病项目(如疫苗项目)中感染SIV并计划实施安乐死的动物。因此，我们不会增加对天然动物的使用；相反，我们将增加原本计划实施安乐死的动物的科学价值。 如果这些研究的结果是成功的，这些可生物降解的纳米颗粒可以用于人类作为传统抗病毒治疗的补充，或用于设计局部杀微生物剂。

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.