Research Project
3489661
Antiviral agents for the treatment for human immunodeficiency virus (HIV-1) are dearly in great need. We have synthesized and done preliminary experiments with a triple helix forming oligonucleotide designed to bind to critical regulatory regions in the proviral genome of HIV-1. Preliminary data show that compound inhibits viral p24 production in a chronically infected monocyte cell line. The primary goal during the Phase I funding period will be to validate the efficacy of this compound in preparation for in vivo pharmacological testing during Phase II. Validation will focus on demonstrating the mechanism of action of the compound and examining the range of in vitro systems in which the compound is active. A secondary goal will be to improve the performance of the compound by selected structural modifications designed to increase affinity and cellular uptake. Modified and unmodified compounds will be tested for improvement in binding affinity, cellular uptake, inhibition of in vitro transcription and efficacy in several chronically infected and acutely infected cell systems to determine theft range of activity.
