LB/CV-N AND RC101 PRIMATE TESTING

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目及 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。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 为了防止艾滋病毒和其他性病的持续传播，必须开发有效的局部杀微生物剂产品并提供使用。该项目建议开发一种组合局部杀微生物剂产品，主要针对预防艾滋病毒的传播，同时也具有预防其他性传播疾病的活性。该产品将由新型化合物（一种肽和一种融合抑制剂）组成，这些化合物相互之间发挥协同作用，从而从尽可能多的角度攻击病原体，同时保持直肠和阴道环境的完整性和微生物群。 产品配方由反复的安全性、毒性和有效性试验（体外、离体和体内）指导。我们的猕猴模型用于确定最可行和最有效的递送机制、化合物可用性和产品安全性。在猕猴模型中的这些实验对于填补实验室和临床研究之间的差距是必不可少的。 总共有12只动物被分配到这个项目。6个已用于评估肽开发研究（RC 101，一种逆转录细胞周期蛋白）。已经进行了旨在研究以阴道膜制剂递送该化合物的可行性的研究。还进行了阴道安全性研究。进一步研究的retrocyclin制定的电影，旨在记录阴道内的存在和分散的活性retrocyclin化合物的计划。 剩余的6只动物用于评估融合抑制剂化合物氰韦林（CV-N），其由表达CV-N的乳酸杆菌递送。到目前为止，我们已经进行了初步研究，旨在调查最有效的传递系统的cyanovirin。在递送能够表达CV-N（体外）的乳酸杆菌后，我们将检测宫颈阴道分泌物中CV-N的存在，作为CV-N可以成功原位表达的证据。

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. In order to prevent the ongoing spread of HIV and other STDs, it is imperative that an effective topical microbicide product be developed and made available for use. This project proposes to develop a combination topical microbicide product, targeted primarily at preventing the transmission of HIV, and also have activity in preventing other STDs. The product will be made up of novel compounds (a peptide and a fusion inhibitor) which exert synergistic effects on one another, thereby attacking pathogens from as many angles as possible, while preserving the integrity and microflora populations of the rectal and vaginal environments. Product formulation is guided by iterative safety, toxicity and efficacy assays (in vitro, ex vivo and in vivo). Our macaque model is used to determine the most feasible and effective delivery mechanisms, compound availability and product safety. These experiments in the macaque model are essential in filling the gap between laboratory and clinical studies. A total of twelve animals have been assigned to this project. Six have been utilized to assess the peptide development studies (RC101, a retrocyclin). Studies designed to investigate the feasibility of delivering this compound in a vaginal film formulation have been conducted. Vaginal safety studies were conducted as well. Further studies of retrocyclin-formulated films, designed to document the intravaginal presence and dispersal of active retrocyclin compound are planned. The remaining six animals have been utilized to assess the fusion inhibitor compound, cyanovirin (CV-N), being delivered by CV-N expressing lactobacilli. To date, we have conducted preliminary studies designed to investigate the most effective delivery system for cyanovirin. After delivery of lactobacilli which are capable of expressing CV-N (in vitro), we will detect CV-N presence in cervicovaginal secretions, as evidence that the CV-N can be successfully expressed in situ.