DrugSearchTool · Innovative FRET-based toolkit for screening of drugs to fight miRNA-related diseases and its use in the development of cancer treatment with miRNA-96 as a therapeutic target

Innovative FRET-based toolkit for screening of drugs to fight miRNA-related diseases and its use in the development of cancer treatment with miRNA-96 as a therapeutic target

The screening of drug candidates against so far undruggable disease states, such as various cancers and certain heart failures, is a vital procedure in the R&D development process in pharmaceutical industry. Efficient screening methods enable a fast and accurate way to find promising drug candidates among myriads of molecules usually available in the molecule libraries of pharmaceutical industry companies. The DrugSearchTool research project carried out by Dr. Anna Wypijewska del Nogal within MSCA-IF in the Wilhelmsson Lab at Chalmers University of Technology, Gothenburg, Sweden, in collaboration with University of Gothenburg (Grøtli Lab) and AstraZeneca (CVRM, BioPharmaceuticals R&D, Gothenburg) resulted in the development of a Förster resonance energy transfer (FRET)-based method to screen for drug candidates for several forms of cancer and heart failure. The method employs light emissive mimics of cellular nucleobases (so-called fluorescent base analogues, FBAs) incorporated into microRNA precursor molecules (pre-miRNA) to report which ligands have a potential to efficiently inhibit miRNA-driven cancerogenesis or heart failure. This innovative approach enables accurate determination of the binding site of a drug candidate within pre-miRNAs, facilitating further optimization of drug structure. The method has been implemented into evaluation of drug candidate libraries for pre-miRNA-21 (upregulated in brain, lung, liver, ovaries, breast, prostate and pancreas cancers) and pre-miRNA-377 (associated to the etiology of heart failure), contributing to the industrial R&D and to the benefit of the society by providing a new tool to help fighting life-threatening malfunctions. Moreover, the method is universal to any RNA/DNA system, which makes it interesting for several academic investigators, working in such fields as biochemistry, biophysics or medicinal chemistry. To date, results acquired during this project have been published in Nucleic Acids Research (2020) and submission of three more manuscripts to well-reputed peer-reviewed journals is envisaged. The project has also been presented in the RadioScience podcast: http://www.radioscience.se/tag/phd-students/.

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