SCREENING ASSAY FOR IDENTIFYING miRNA-SPECIFIC DRUG COMPOUNDS

摘要

The present invention relates to a method for identifying miRNA (microRNA)-modulating compounds by contacting a compound of interest with a cell comprising (i) a “miRNA-specific module” that reports specific miRNA target sequence binding by means of a first reporter product; (ii) a “non-specific RNAi module” that reports altered expression of one or more endogenous miRNAs with baseline expression levels in the cell (“non-specific miRNA markers”) by means of a second reporter product; and optionally (iii) a “gene expression module” that reports global changes in gene expression; and subsequent detection of changes in reporter product expression. The advantage of this method is that non-specific miRNA- and/or RNAi-effects of the compound of interest are detected and false positive results due to the structural similarity of different miRNAs and the commonly shared maturation pathway for most miRNAs are substantially reduced over conventional miRNA screening assays.