Today, 33.4 million people worldwide are living with HIV/AIDS. HIV is the leading cause of death in U.S. adults aged 25-44 years. Despite the effectiveness of current anti-retroviral chemotherapies, treatment failure occurs at rates as high as 20-50% due to drug toxicity and development of drug resistance in the virus. The overall objective of this project is to identify potent anti-HIV-1 antisense, ribozyme, and decoy agents and develop these nucleic acid-based anti-HIV agents as therapeutics for the treatment of HIV infection. To achieve this objective, the following specific aims are to be accomplished. Aim 1. Construct and characterize anti-HIV antisense, ribozyme, and decoy libraries. Aim 2. Screen the anti-HIV libraries for effective anti-HIV antisense, ribozyme, and decoy clones. Aim 3. Identify the nucleotide sequences of the effective anti-HIV clones. Aim 4. Confirm their anti-HIV activities using synthetic antisense, ribozyme, and decoy agents. Aim 1 will be completed and Aim 2 initiated in Phase I of this project. Aim 2, 3, and 4 will be completed in Phase II (to be submitted) of this project. Since these anti-HIV libraries are constructed directly from the complete HIV-1 cDNA, we believe that novel and highly effective anti-HIV antisense, ribozyme, and decoy molecules can be identified. These effective anti-HIV agents can then be developed as therapeutics, individually or in combination, or used in gene therapy, for the control and prevention of HIV infection. PROPOSED COMMERCIAL APPLICATIONS: This work will allow development of potent anti-HIV antisense, ribozyme, and decoy therapeutics.
Thesaurus Terms: antiAIDS agent, antisense nucleic acid, biotherapeutic agent, drug design /synthesis /production, nucleic acid chemical synthesis, nucleic acid sequence, ribozyme AIDS therapy, genetic library, transcription factor cell line, genetic screening, molecular cloning, transfection
