Abstract
| Grant Number: | 5R44DK061837-04 |
| Project Title: | A High-Throughput Cell-based Drug Discovery System |
Abstract:
DESCRIPTION (provided by applicant): This Phase II SBIR project is focused at the development of a high-throughput screening method and instrument for drug discovery using miniaturized, cell-based assays. For developing new drugs against complex diseases such as diabetes, cancer and neurological and cardiovascular disorders, high throughput screening using cell-based assays will be essential. Miniaturization of cell-based assays for automation and reduced costs is required. GeneCard-HTS enables drug discovery using adherent cell-based assays. During the Phase I project, the feasibility of the GeneCard approach was demonstrated using apoptosis assays. A prototype instrument to automate GeneCard assay process was developed and assembled. During Phase II, the versatility and flexibility of the GeneCard platform will be investigated by performing other cell-based assays used in drug discovery. The proposed plan investigates the following three specific aims:
1. Build a high-throughput screening prototype system based on GeneCard technology (GeneCard-HTS).
2. Miniaturize multiple cell-based assays for GeneCard-HTS platform. We will miniaturize four commonly used drug discovery assays in the GeneCard-HTS platform, i) Apoptosis assays using the Mitosensor reagents, ii) cell-based kinase assays, iii) fluorescent cytotoxicity assays, and iv) gene expression profiling assays. We will measure the performance of these assays in GeneCard-HTS platform and compare with performance obtained at present.
3. Validate GeneCard-HTS by cell-based screening of compound libraries. In order to validate the Genecard-HTS system, we will perform screening of a 5,000 compound focused library using cell-based kinase and apoptosis assays. We will measure validation parameters such as system lifetime, operating temperature and humidity range, inter- and intra- assay variability, and day-to-day variability.
Commercial applications of the proposed system include pharmaceutical and biotechnoiogy drug discovery. Further integration of the instrument based on design specifications prepared in Phase I will be performed. Screening of drug compound libraries to identify potential lead compounds will be performed.
Thesaurus Terms:
biomedical automation, biomedical equipment development, drug discovery /isolation, drug screening /evaluation, high throughput technology, method development, microarray technology, miniature biomedical equipment
apoptosis, cell mediated lymphocytolysis test, chemical registry /resource, gene expression profiling, pharmacokinetics
bioengineering /biomedical engineering, biotechnology, computer program /software
| Institution: | GENOME DATA SYSTEMS, INC. |
| HAMILTON, NJ 08610 |
| Fiscal Year: | 2006 |
| Department: | |
| Project Start: | 15-JUN-2002 |
| Project End: | 30-APR-2008 |
| ICD: | NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES |
| IRG: | ZRG1 |
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