NOVEL ASSAY FOR MEASURING THE INHIBITION OF HIV-1 ENTRY

抗逆转录病毒疗法为艾滋病毒/艾滋病提供了巨大的临床益处 患者然而，治疗失败是常见的，主要是由于出现 抵抗病毒。HIV-1逆转录酶的商业敏感性检测 蛋白酶抑制剂在日常生活中发挥着越来越重要的作用， HIV-1感染者的管理。针对HIV-1不同方面的药物 复制，主要是病毒进入，也是迫切需要的。实用分析， 支持开发进入抑制剂并检测患者体内的耐药病毒 都没有。 预防性疫苗将是对付艾滋病流行病的有力武器。 今天最有希望的候选物被设计为引发中和抗体， 阻止病毒进入。候选疫苗的评估需要大规模的临床试验。 因此，用于测量病毒中和活性的高通量测定法是可行的。 迫切需要。 在第一阶段，我们将证明一种新的测定抑制的可行性， 病毒附着和进入的过程我们将构建表达HIV-1包膜蛋白的载体 蛋白质和含有用于测量病毒的报告基因的逆转录病毒载体 复制的将使用包膜反式互补病毒感染细胞系 表达HIV-1受体的细胞这种分析将成为一种有价值的工具， 表征候选药物，优化患者治疗，并支持疫苗 发展 拟定商业应用： 我们打算开发一种快速、灵敏的表型测定法来测量 HIV-1对多种病毒进入抑制剂的敏感性。本试验将 补充了现有的商业检测方法， 转录酶和蛋白酶抑制剂。该检测试剂盒将销售给医生， 协助艾滋病毒/艾滋病患者的护理，以及制药公司支持 他们的药物和疫苗开发计划。

Antiretroviral therapy has provided tremendous clinical benefit to HIV/AIDS patients. However, treatment failure is common and due mostly to emergence of resistant viruses. Commercial susceptibility assays for HIV-1 reverse transcriptase and protease inhibitors are playing an increasingly important role in the routine management of HIV-1 infected patients. Drugs that target different aspects of HIV-1 replication, primarily virus entry, are urgently needed as well. Practical assays to support the development of entry inhibitors and detect resistant viruses in patients are not available. A prophylaxis vaccine would be a powerful weapon against the AIDS pandemic. Today's most promising candidates are designed to elicit neutralizing antibodies that block virus entry. Evaluation of vaccine candidates requires large clinical trials. Consequently, high-throughput assays for measuring virus neutralization activity are urgently needed. In phase I we will demonstrate feasibility of a novel assay that measures inhibition of viral attachment and entry. We will construct a vector to express HIV-1 envelope proteins and a retroviral vector that contains a reporter gene for measuring viral replication. Envelope trans-complemented viruses will be used to infect cell lines that express HIV-1 receptors. This assay will become a valuable tool for characterizing drug candidates, optimizing patient treatment, and supporting vaccine development. PROPOSED COMMERCIAL APPLICATION: We intend to develop a rapid, sensitive, phenotypic assay to measure the susceptibility of HIV-1 to a wide variety of virus entry inhibitors. This assay will supplement existing commercial assays that measure susceptibility to reverse transcriptase and protease inhibitors. The assay will be marketed to physicians to assist in HIV/AIDS patient care, as well as pharmaceutical companies to support their drug and vaccine development programs.