Biosensing of miRNA and detection of its drug-interactions
MicroRNAs (miRNAs) are short, single-stranded RNAs that have fundamental roles in almost every aspect of biology. These endogenous miRNAs regulate gene expression in a sequence specific fashion by binding the 3’ untranslated region of target messenger RNA (mRNA) resulting in down- or up-regulation of the target genes. Increasing evidence also suggests that miRNAs contribute to a spectrum of human diseases, cancer as well as inflammatory and cardiovascular diseases, implying that modulation of miRNA expression may serve as a novel therapeutic modality for such diseases. In this project we will investigate and develop two invaluable detection methods for miRNAs: 1) A biosensor system to specifically detect specific miRNAs using complementary DNA modified with fluorescent base analogues (FBAs); 2) An in vitro assay suitable for monitoring small molecule binders, (candidate) drugs, to precursor miRNA modified with fluorescent RNA base analogues. With their internal position in DNA and RNA base-stacks, FBAs comprise an attractive alternative to external probes, which may alter interactions between the target miRNA and the complementary nucleic acid or the (candidate) drug. Here we will use our vast experience in FBAs and in the use of fluorescence techniques to provide pharmaceutical industry, hospital laboratories and academia with unprecedented miRNA-methods.
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- Swedish Foundation for Strategic Research (SSF) (Non Profit, Sweden)