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RNAatHD

Development of a high-resolution method to monitor structural changes of regulatory RNAs and therapeutic oligo-nucleotides directly in-cell.

Total Cost €

EC-Contrib. €

Partnership

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Outcomes and
results

RNAatHD project word cloud

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

of scope molecular structures exploited unspecific nuclear spectrum regulatory cells biology industry er unraveled interactions understand nmr mir resolution candidate diagnostics complexity group broad monitor synthetic 34a tested benefit slow concentration researcher host dynamics poorly sense candidates resonance comprehension therapeutics astrazeneca aons micrornas academia diseases oligonucleotides cell structural cancer lack magnetic health solving off interface vast occurring besides time drugs structure combining molecule rnas drug demonstrated overcoming mrnas aon link biological mirnas mirna living cellular intermolecular messenger regulators fact mrna leader progress opportunity mechanism anti function nucleotides first master

Project "RNAatHD" data sheet

The following table provides information about the project.

Coordinator	KAROLINSKA INSTITUTET Organization address address: Nobels Vag 5 city: STOCKHOLM postcode: 17177 website: www.ki.se 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	Sweden [SE]
Project website	http://petzoldlab.com
Total cost	185˙857 €
EC max contribution	185˙857 € (100%)
Programme	1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
Code Call	H2020-MSCA-IF-2016
Funding Scheme	MSCA-IF-EF-ST
Starting year	2017
Duration (year-month-day)	from 2017-05-01 to 2019-04-30

Partnership

Take a look of project's partnership.

#	participants	country	role	EC contrib. [€]
1	KAROLINSKA INSTITUTET KAROLINSKA INSTITUTET Organization address address: Nobels Vag 5 city: STOCKHOLM postcode: 17177 website: www.ki.se contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	SE (STOCKHOLM)	coordinator	185˙857.00

Map

Project objective

MicroRNAs (miRNAs) are master regulators in cells with a complexity yet to be unraveled. By targeting one or more messenger RNAs (mRNAs) they affect a vast number of biological processes and are associated with a broad spectrum of diseases, including cancer. This makes them potential candidates for cancer-diagnostics and -therapeutics. This opportunity can only be fully exploited by a better comprehension of how and when each mRNA is targeted by a miRNA, a fact, which is currently still poorly understood. Besides regulatory RNAs, synthetic “anti-sense” oligonucleotides (AONs) are currently tested as cancer drugs. Progress in this field has been slow due to unspecific off-target-effects i.e. the lack of understanding, of the mechanism of AONs targeting mRNAs. This project focuses on overcoming this lack of knowledge of the targeting process. To understand the intermolecular interactions occurring in the cell we will, for the first time, monitor the molecular structure and structural changes (dynamics) of nucleotides (miRNAs as well as AONs) in the living cell, and link these in-cell structures to the molecule’s targeting function. Combining existing knowledge of the host in structural and molecular biology of miRNAs with the experience in methods development in Nuclear Magnetic Resonance (NMR) of the experienced researcher (ER), we will develop a set of robust and reliable in-cell NMR methods to determine cellular concentration, structure and dynamics within the cell at high resolution. The scope of the method will be demonstrated on: (i) a miRNA, miR-34a, which targets more than 50 different mRNAs, related to cancer and other cellular processes, as well as (ii) an AON drug candidate in collaboration with AstraZeneca. This project will benefit drug development against various diseases and will enable the ER to contribute to solving today's health problems and develop further towards becoming a future group leader on the interface of research in academia and industry.

Publications

List of publications.
year	authors and title	journal	last update
2019	Judith Schlagnitweit, Sarah Friebe Sandoz, Aleksander Jaworski, Ileana Guzzetti, Fabien Aussenac, Rodrigo J. Carbajo, Elisabetta Chiarparin, Andrew J. Pell, Katja Petzold Observing an antisense drug complex in intact human cells by inâ€cell NMR published pages: , ISSN: 1439-4227, DOI: 10.1002/cbic.201900297	ChemBioChem	2019-09-25
2019	Maja MaruÅ¡iÄ, Judith Schlagnitweit, Katja Petzold RNA dynamics by NMR published pages: , ISSN: 1439-4227, DOI: 10.1002/cbic.201900072	ChemBioChem	2019-09-25

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