The purpose of this contract is to support the Basic Research and Development Program in achieving its goals of developing and standardizing biological and biochemical assays for the confirmatory testing of potential therapies for the treatment of AIDS and the opportunistic infections associated with AIDS and in generating, characterizing and standardizing critical reagents required for these evaluations. The program requires facilities and resources needed to support its activities. One of the functions of the Program is to facilitate drug discovery and preclinical development of agents showing initial activities against HIV. The Program requires facilities to confirm activities against HIV, extend testing to other retroviruses and provide in vitro models of AIDS using HIV or other appropriate retroviruses to support the NCDDG-funded research. The specific objective of the studies proposed in the contract are to: (1) develop new and evaluate published or BRDP suggested/provided quantitative assays for infectious HIV or SIV, (2) design, develop, standardize, validate and perform cell culture based assays for the evaluation and confirmation of potential anti-HIV agents, (3) design, develop, and perform cell culture based evaluations to augment the standardized anti-HIV assays, (4) design, develop, standardize, validate and perform biochemical assays to determine the molecular mechanism of action of agents with anti-HIV assays, (5) compare and analyze the data obtained in the assays (in vitro, biochemical) or clinical results (if available) with those obtained by other researchers using same or similar therapies, (6) design, develop and utilize expression systems for the large scale production and purification of RNA of defined sequence, and (7) provide facilities and resources to conduct the above- stated work in an efficient, effective, safe and cost-effective manner.
| Buckheit Jr, R W; Fliakas-Boltz, V; Yeagy-Bargo, S et al. (1995) Resistance to 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine derivatives is generated by mutations at multiple sites in the HIV-1 reverse transcriptase. Virology 210:186-93 |
| Buckheit Jr, R W; Fliakas-Boltz, V; Decker, W D et al. (1995) Comparative anti-HIV evaluation of diverse HIV-1-specific reverse transcriptase inhibitor-resistant virus isolates demonstrates the existence of distinct phenotypic subgroups. Antiviral Res 26:117-32 |
