LabAutomation 2006 - SLAS

MP13
Bruce Seligmann
High Throughput Genomics, Inc.
Tucson Arizona
bseligmann@htgenomics.com
Where Laboratory Technologies Emerge and Merge
Co-Author(s)
Ihab Botros, Matt Rounseville, Ralph Martel
High Throughput Genomics, Inc.
Stephen Felder, Rick Kris
Nuvogen, LLC
High Throughput Cell and Tissue-Based Gene Expression Assay for Target Validation,
Screening and EC50-Based Profiling and Optimization of Efficacy, Specificity,
Metabolism and Safety
Gene expression assays have provided low quality data and low sample throughput compared to conventional biochemical (e.g. enzyme)
drug discovery assays. Furthermore, whole cell screening assays typically have problematically high false positive hit rates and when
whole cell assays are used for lead optimization there is uncertainty whether the mechanism of action giving rise to the measured cellular
response remains the same between analogs. Consequently, gene expression-based drug discovery programs are uncommon. The
ArrayPlate quantitative Nuclease Protection Assay (qNPATM) gene expression platform enables a paradigm shift in mainstream drug
discovery and profiling. Multiplexed, measuring 16 genes/well of a 96-well microplate or 4 genes/well of a 384-well microplate, qNPA
delivers high content (1536 datapoints) capable of distinguishing and tracking multiple mechanisms of action. A simple, robust lysis-only
protocol permits high sample throughput (cells, frozen/fresh/fixed tissue, whole organisms) and produces “biochemical” quality data: whole
cell assay CV’s of 5 to 10%, repeatable day-to-day within 5%, repeatable lab-to-lab. Thus, weak activity (