OLIGONUCLEOTIDES INHIBITION OF HIV-1 INTEGRASE

人类免疫缺陷病毒感染的有效治疗 仍然难以捉摸，部分原因是受感染的长寿命细胞 为病毒提供了一个蓄水池。目前可用的抗逆转录病毒药物 药物是逆转录酶抑制剂。尽管他们取得了成功， 目前，这些化合物的用途有限，因为它们的毒性 以及缺乏行动对传染性病毒的产生没有影响 在含有整合前病毒的细胞中。因此，重要的是要 针对生活中其他重要因素的替代方法 病毒的循环。这种方法将涉及以化合物为目标。 干扰HIV生命周期中的病毒整合酶。 开发临床可耐受的HIV抑制剂将整合 为抗逆转录病毒治疗提供了广泛的 应用范围包括与当前 可用于急性HIV感染的逆转录酶抑制剂和 作为针对慢性感染细胞中HIV-1的药物。在这个项目中 我们建议设计针对HIV的靶向抑制剂并进行评估 使用体外检测系统检测它们的治疗效果。前景看好的人 化合物将在组织培养和体内试验中进一步评估 系统。

Effective therapy for human immunodeficiency virus (HIV) infection remains elusive, partly due to the fact that infected long lived cells provide a reservoir for the virus. Currently available anti retroviral agents are reverse transcriptase inhibitors. In spite of their success, these compounds, the moment, have limited utility because their toxicity and lack of action have no effect on the production of infectious virus in cells harboring integrated provirus. Therefore, it is important to alternative approaches which target other factors important to the life cycle of the virus. The such approach would involve targeting compounds which interfere with the viral integrate enzyme in the HIV life cycle. Development of clinically tolerable inhibitors of HIV integrate would have profound implications for anti retroviral therapy by offering a wide range of application including potential synergy with the currently available reverse transcriptase inhibitors in acute HIV infections and as agents to target HIV-1 in chronically infected cells. In this project we propose to design inhibitors target to HIV integrate and evaluate their therapeutic utility using in vitro assay systems. The promising compounds will further be evaluated in tissue culture and in vivo assay systems.