OLIGONUCLEOTIDES INHIBITION OF HIV-1 INTEGRASE

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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.