MOLECULAR AND CELLULAR TRANSPORT IN MUCUS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 研究中心，而研究中心不一定是研究者所在的机构。 目前，全世界有超过4000万人持续感染HIV-1。与人类感染艾滋病毒类似，亚洲猕猴感染SIV会导致慢性疾病，最终导致艾滋病。恒河猴明确的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、病毒的细胞嗜性、病毒复制模式、疾病进展和宿主免疫应答的性质。此外，SIV/猕猴模型是重要的，因为病毒暴露的时间、途径和数量的知识是已知的，用于感染猕猴的病毒库是良好表征的，并且在整个感染过程中能够频繁地对重要组织（血液、淋巴结、粘膜部位等）进行采样。 目前在艾滋病领域的主要研究方向之一是确定新的治疗方法，这将导致减少或抑制感染个体的病毒载量。该项目的目标是确定携带SIVmac特异性小干扰RNA（siRNA）的可生物降解聚（乳酸-羟基乙酸）聚合物（PLGA）纳米颗粒的体内疗效。 为了主要靶向受感染的细胞，颗粒还将用抗CD 4抗体包被。这项研究将使用已经感染SIV的恒河猴。 该项目第一年的动物已经可以从我们实验室进行的其他研究中获得。 在随后的几年里，我们建议使用来自SNPRC其他艾滋病项目（如疫苗项目）的动物，这些动物感染了SIV并计划进行安乐死。 因此，我们不会增加对幼稚动物的使用;相反，我们将增加动物的科学价值，否则将被安排安乐死。 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的抗病毒治疗的补充，或用于局部杀微生物剂的设计。

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.