AN SIRNA-BASED MICROBICIDE TO PREVENT HIV TRANSMISSION

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 该项目是与Lieberman博士（哈佛）的合作研究，旨在开发基于小干扰RNA（siRNA）技术的有效杀微生物剂。 我们还在开发疱疹病毒传播模型，以确定这是否也可用于开发预防性杀微生物剂。 迄今为止，我们已经表明恒河猴对HSV-1易感，并在阴道上皮中形成溃疡、微泡和炎症，并在感染后数周至数月表达HSV-1基因。 我们还测试了针对宿主nectin（疱疹结合受体）的siRNA技术，并显示当应用于猕猴时，阴道上皮细胞中的nectin表达发生显著下调。我们目前正在重复这项实验，使用仔细收集的活组织检查来确定nectin下调的分布，看看这是否可以防止HSV-1传播。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This program project is a collaborative study with Dr. Lieberman (Harvard) to develop an effective microbicide based on small interfering RNA (siRNA) technology. We are also developing a model of herpesvirus transmission to determine if this can also be used to develop preventative microbicides. To date we have shown rhesus macaques are susceptible to HSV-1 and develop ulcerations, microvesicles, and inflammation in the vaginal epithelium and express HSV-1 genes for several weeks to months after infection. We have also tested siRNA technology against host nectin (the herpes binding receptor) and shown substantial downregulation occurs in the expression of nectin in vaginal epithelial cells when applied to macaques. We are currently repeating this experiment using carefully collected biopsies to determine the distribution of the downregulation of nectin to see if this can prevent against HSV-1 transmission.