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TRIGGDRUG SIGNED

Reactions That Translate mRNA into Drug-like Molecules

Total Cost €

0

EC-Contrib. €

0

Partnership

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 TRIGGDRUG project word cloud

Explore the words cloud of the TRIGGDRUG project. It provides you a very rough idea of what is the project "TRIGGDRUG" about.

death    reactive    acyl    inside    translate    deregulated    formed    rewire    expression    cells    small    protein    nucleic    peptidomimetics    sequence    cancer    provides    reactions    acid    template    cure    triggers    gene    alkylidene    therapy    triggered    output    caused    photodynamic    patient    idea    synthesis    read    tool    active    drug    mutation    recognition    turnover    rna    advantage    perturbation    peptides    express    accordingly    activated    amplification    inhibition    hijack    disease    promoted    induce    molecules    translocation    reactivity    cope    transcriptome    inhibitors    reaction    generation    apoptosis    molecular    2040    identity    chemical    nutshell    chemistry    mrna    aberrantly    cellular    couple    look    copy    synergy    opportunity    instructors    kinase    sequencing    cell    validated    harnessed    transfer    form    how    expressed    single    worlds    eliminate    personalized    data    molecule    healthy    genes   

Project "TRIGGDRUG" data sheet

The following table provides information about the project.

Coordinator
HUMBOLDT-UNIVERSITAET ZU BERLIN 

Organization address
address: UNTER DEN LINDEN 6
city: BERLIN
postcode: 10117
website: www.hu-berlin.de

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Germany [DE]
 Total cost 2˙470˙400 €
 EC max contribution 2˙470˙400 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-ADG
 Funding Scheme ERC-ADG
 Starting year 2016
 Duration (year-month-day) from 2016-01-01   to  2020-12-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    HUMBOLDT-UNIVERSITAET ZU BERLIN DE (BERLIN) coordinator 2˙470˙400.00

Map

 Project 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.

 Publications

year authors and title journal last update
List of publications.
2018 Jasmine Chamiolo, Ge‐min Fang, Felix Hövelmann, Dhana Friedrich, Andrea Knoll, Alexander Loewer, Oliver Seitz
Comparing Agent‐Based Delivery of DNA and PNA Forced Intercalation (FIT) Probes for Multicolor mRNA Imaging
published pages: , ISSN: 1439-4227, DOI: 10.1002/cbic.201800526
ChemBioChem 2019-04-18

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