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Unravelling extracellular vesicle heterogeneity to inspire improved therapeutic RNA delivery systems

Objective

The growing number of classes of RNA therapeutics, including siRNA, mRNA and RNA components of the CRISPR/Cas9 machinery, hold the promise of providing new treatment possibilities for almost any disease. However, these interventions require delivery of therapeutic RNA to their final intracellular targets in diseased cells, and delivery efficiency by current RNA nanocarriers is unsatisfactory.

Endogenous nanoparticles called extracellular vesicles (EVs) have emerged as promising novel RNA delivery systems, due to their intrinsic ability to transfer biological cargo between cells in a selective manner. In fact, with my ERC StG, I have shown that EVs outperform synthetic carriers in terms of RNA delivery efficiency. However, EVs are a heterogeneous population of vesicles that differ in their targeting and cargo delivery properties, which forms a hurdle for the design of EV-based delivery systems. As methods to separate EV subpopulations and study their characteristics individually are lacking, a fundamentally different approach to address this hurdle is necessary.

The aim of UNRAVEL is to reveal how variations in EV composition lead to specialized subpopulations with unique delivery features. Using this knowledge, I will develop the first biomimetic class of EV-inspired synthetic RNA delivery systems. I will pursue three objectives:
1) Identify EV subpopulations with unique targeting and RNA delivery properties using a novel EV barcoding strategy
2) Define these EV subpopulations in terms of unique surface properties, intracellular trafficking and cargo release
3) Apply this knowledge to improve synthetic RNA delivery systems by incorporating molecular features from EV subpopulations

This work will significantly advance our understanding of the natural targeting and RNA delivery mechanisms of EV subpopulations and may result in a new generation RNA delivery system based on EV mimetics. In turn, this will allow more widespread application of RNA therapeutics.

Fields of science (EuroSciVoc)

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Keywords

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Programme(s)

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Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2023-COG

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Host institution

UNIVERSITAIR MEDISCH CENTRUM UTRECHT
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 2 000 000,00
Address
HEIDELBERGLAAN 100
3584 CX Utrecht
Netherlands

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Activity type
Higher or Secondary Education Establishments
Links
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 2 000 000,00

Beneficiaries (1)

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