Innovating Works

TRIGGDRUG

Financiado
Reactions That Translate mRNA into Drug like Molecules
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 identi... 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. ver más
31/12/2020
UBER
2M€
Duración del proyecto: 65 meses Fecha Inicio: 2015-07-24
Fecha Fin: 2020-12-31

Línea de financiación: concedida

El organismo H2020 notifico la concesión del proyecto el día 2020-12-31
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
ERC-ADG-2014: ERC Advanced Grant
Cerrada hace 10 años
Presupuesto El presupuesto total del proyecto asciende a 2M€
Líder del proyecto
HUMBOLDTUNIVERSITAET ZU BERLIN No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 4-5