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 病人。然而，治疗失败是很常见的，主要是由于出现了 抗药性病毒。HIV-1逆转录酶的商业药敏试验 而蛋白水解酶抑制剂在日常生活中扮演着越来越重要的角色 HIV-1感染患者的管理。针对HIV-1不同方面的药物 也迫切需要复制，主要是病毒输入。实用的化验方法 支持进入抑制剂的开发，并在患者中检测耐药病毒 都不可用。 预防疫苗将是对抗艾滋病大流行的有力武器。 今天最有希望的候选人被设计成诱导中和抗体 阻止病毒输入。对候选疫苗的评估需要进行大规模的临床试验。 因此，用于测量病毒中和活性的高通量检测方法有 急需之物。 在第一阶段，我们将论证一种新的检测抑制的可行性。 病毒依附和进入。我们将构建一个表达HIV-1包膜的载体 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。包膜反式互补病毒将用于感染细胞系 表达HIV-1受体的生物。这项测试将成为一种有价值的工具 确定候选药物、优化患者治疗和支持疫苗 发展。 建议的商业应用： 我们打算开发一种快速、灵敏的表型检测方法来检测 艾滋病毒-1对多种病毒进入抑制剂的敏感性。这个化验结果会 补充现有的测量逆转敏感性的商业检测方法 转录酶和蛋白酶抑制剂。该化验结果将向医生销售，以 协助艾滋病毒/艾滋病患者的护理，以及对制药公司的支持 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.