EXPRESSION PATTERN SCREENING FOR DRUG DISCOVERY

提出了开发高通量多mRNA测定法用于筛选大量化合物以发现影响基因表达模式的潜在药物。可以在96孔板的每个孔内一次全部测试一组疾病相关基因和对照基因的表达。研究人员可以评估96种不同的候选药物如何影响每个平板中这些基因的表达模式。该技术将解决制药行业尚未满足的需求-有效利用新的基因组学信息。这将允许测试更多的基因靶点，包括新鉴定的基因，并将提供更多关于选择性和特异性的信息。专有方法将允许DNA阵列技术用于高通量多mRNA测定，通过增加灵敏度和可靠性。初步结果证明了可行性。DNA阵列可以应用于每个孔内并保持杂交特异性。该方法对于在96孔板的一个孔内生长的细胞中以每个细胞一个mRNA分子表达的基因足够灵敏。我们建议进一步改进这些方法，以形成一种可靠和灵敏的筛选技术，用于发现调节基因表达模式的新药。拟议的商业应用：在制药工业中，对用于筛选大量化合物以发现影响基因表达模式的潜在药物的高通量多mRNA测定的需要是绝对必要的。该试验预计将缩短新药发现周期1-2年。

Development of a high throughput multiple mRNA assay is proposed for screening large numbers of compounds to discover potential drugs that affect patterns of gene expression The expression for a group of disease- related and control genes can be tested all at once within each well of a 96- well plate. Investigators can evaluate how 96 different drug candidates affect the expression pattern for these genes m each plate. This technology will address an unmet need of the pharmaceutical industry - to make efficient use of novel genomics information This will allow testing of more gene targets including newly identified genes, and will provide more information about selectivity and specificity. Proprietary methods will allow DNA array technology to be used for the high throughput multiple mRNA assay, by increasing sensitivity and reliability. Preliminary results demonstrate feasibility. DNA arrays can be applied within each well and retain hybridization specificity. The method is sensitive enough for genes expressed at one mRNA molecule per cell from the cells grown within one well of a 96-well plate. We propose to improve the methods further to form a reliable and sensitive screening technology for discovering new drugs that modulate gene expression patterns. PROPOSED COMMERCIAL APPLICATIONS: The need for a high throughput multiple mRNA assay for screening large numbers of compounds to discover potential drugs that affect patterns of gene expression is an absolute necessity in the pharmaceutical industry. The assay is expected to cut 1-2 years off the new drug discovery cycle.