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OBSERVE SIGNED

Overcoming cellular barriers to therapeutic RNA delivery using extracellular vesicles

Total Cost €

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EC-Contrib. €

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Partnership

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Project "OBSERVE" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITAIR MEDISCH CENTRUM UTRECHT 

Organization address
address: HEIDELBERGLAAN 100
city: UTRECHT
postcode: 3584 CX
website: www.umcutrecht.nl

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 Netherlands [NL]
 Total cost 1˙500˙000 €
 EC max contribution 1˙500˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2019-STG
 Funding Scheme ERC-STG
 Starting year 2020
 Duration (year-month-day) from 2020-02-01   to  2025-01-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITAIR MEDISCH CENTRUM UTRECHT NL (UTRECHT) coordinator 1˙500˙000.00

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 Project objective

RNA-based therapeutics, including siRNA, miRNA, mRNA and CRISPR/Cas9 components, have unprecedented therapeutic potential and hold the promise of treating any disease with a genetic component. However, inefficient delivery into diseased cells hinders their clinical progress. Consequently, there is an urgent need for novel, original approaches to overcome the delivery challenges.

Recently, an endogenous RNA transport system has emerged, based on the release and uptake of extracellular vesicles (EVs). EVs are naturally equipped to transfer RNA molecules to other cells in a functional and selective manner. Furthermore, I have recently demonstrated that EVs deliver RNA more efficiently than state-of-the-art synthetic RNA nanocarriers. Thus, EVs hold promise as a new paradigm for RNA delivery. However, the mechanisms underlying EV-mediated RNA transfer are unknown, and reproducible methods for efficient loading of EVs with therapeutic RNA are lacking.

The aim of my proposal is to (1) elucidate the mechanisms underlying EV internalization and processing that lead to the functional delivery of their RNA content and (2) radically improve the loading efficiency of EVs for therapeutic RNA delivery. To realize this, I will: 1) Identify genes and pathways involved in EV-mediated RNA transfer using a novel CRISPR/Cas9-based RNA delivery reporter system. 2) Systematically compare uptake and intracellular trafficking of EVs and synthetic nanocarriers. 3) Design a novel and improved method to load EVs with therapeutic RNA. 4) Demonstrate the effect of EV-mediated delivery of therapeutic RNA in a murine model of myocardial infarction.

The outcome of this research will fundamentally advance our understanding of the cellular processes enabling EV-mediated RNA transfer, which is of crucial importance for the development of EV-based and EV-inspired delivery systems. This research will accelerate clinical translation of an entire new class of therapeutics based on EVs and RNA.

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The information about "OBSERVE" are provided by the European Opendata Portal: CORDIS opendata.

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