Objective How could a molecular cancer therapy look like in 2040? In cancer, gene expression is deregulated due to amplification, mutation and translocation of genes. Next generation RNA sequencing provides us with the opportunity to identify the number and identity of the gene products aberrantly expressed in a patient. But do we have methods that take advantage of the personalized sequence data? In this research project we propose the idea to use the RNA molecules expressed upon disease-type gene expression as instructors for the chemical synthesis of drug-like molecules that cure the disease. Accordingly, drug-like molecules would only be formed in those cells that express the disease-specific RNA molecules. Such a personalized molecular therapy would eliminate side effects caused by unwanted perturbation of healthy cells. The idea to use cellular RNA molecules as triggers for drug synthesis requires methods that couple RNA recognition with a change of chemical reactivity. Reactive molecules must be able to “read” and “translate” the sequence of a RNA molecule into a drug-like output. We will develop mRNA-triggered reactions that i) proceed with turnover in template to cope with low mRNA copy numbers and ii) allow the single-step synthesis of highly active drug-like molecules to address deregulated protein targets inside cancer cells. To achieve this aim, we will advance chemical acyl transfer and alkylidene transfer reactions. The reactions on disease-specific mRNA will form peptides/peptidomimetics/small molecule-based kinase inhibitors which will induce apoptosis in cancer cells. We will target validated drug targets. Synergy between the nucleic acid and protein worlds will be harnessed. Furthermore, we will develop a RNA-promoted reaction with turnover beyond product inhibition. This will enable a transcriptome-activated photodynamic therapy. In a nutshell, we will develop a chemistry-based tool to hijack disease mRNA and rewire the cell death program. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsnatural sciencesbiological sciencesbiochemistrybiomoleculesnucleic acidsmedical and health sciencesclinical medicineoncologynatural sciencesbiological sciencesgeneticsRNAnatural scienceschemical sciencesorganic chemistryamines Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-ADG-2014 - ERC Advanced Grant Call for proposal ERC-2014-ADG See other projects for this call Funding Scheme ERC-ADG - Advanced Grant Host institution HUMBOLDT-UNIVERSITAET ZU BERLIN Net EU contribution € 2 470 400,00 Address UNTER DEN LINDEN 6 10117 Berlin Germany See on map Region Berlin Berlin Berlin Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 2 470 400,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all HUMBOLDT-UNIVERSITAET ZU BERLIN Germany Net EU contribution € 2 470 400,00 Address UNTER DEN LINDEN 6 10117 Berlin See on map Region Berlin Berlin Berlin Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 2 470 400,00
