SBIR Phase II: New Labeling Reagents for Genetic Analysis

This Small Business Innovation Research Phase II project aims to develop new, sensitive, accurate, and reliable detection methods for measuring genomic DNA or RNA samples isolated from living cells. The intellectual merit of this project lies in the development of new detection methods that are essential for improving high-throughput genomic microarray analyses of gene activity. Problems with current microarray and genomic analysis techniques, including hybridization perturbation, slow enzymatic labeling methods using expensive labeled nucleotides and sequence dependence, are solved using a direct labeling approach. These new systems will provide the detection tools needed to advance the promising pharmaceutical, research and diagnostic uses of genomic analysis to determine the pattern of gene expression in disease or upon therapeutic treatment. Marker Gene Technologies, Inc. has established the feasibility of these detection methods by preparing new ultrasensitive fluorescent labeling reagents and developing protocols for directly labeling DNA or RNA samples isolated from live cells. These reagents are able to efficiently and sensitively label oligonucleotides for high-throughput microarray analysis. In Phase II these systems will be validated by further analysis of the fluorescent labeling methods and characterization of their ability to monitor changes in gene expression upon application of drugs or other bioactive compounds or in response to biological changes in cell function or disease, in a cell-specific manner. The broader impacts of this project include development and commercialization of new methods for rapid screening of genomic expression patterns in response to specific drug application in normal cells and tissues as well as in disease, bacterial or viral infections. These methods are a significant improvement over existing technologies by using a direct labeling approach that is quicker, more accurate and more cost-effective. These systems will be marketed to the pharmaceutical and diagnostics industries for high-throughput pre-clinical screening of drug efficacy by comparative cellular genomic analysis. In addition, existing collaborations with industrial and research partners assure quick commercial development of the technology. The combined techniques will improve U.S. competitiveness in the burgeoning genomic analysis field as well as in pharmaceutical therapeutic drug development and lead to further job creation based on both the products and systems developed.