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UNRAVEL

Financiado

Unravelling extracellular vesicle heterogeneity to inspire improved therapeutic...

Unravelling extracellular vesicle heterogeneity to inspire improved therapeutic RNA delivery systems 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 interventio... ver más

31/01/2030

UMC UTRECHT

2M€

Presupuesto del proyecto: 2M€

Líder del proyecto

UNIVERSITAIR MEDISCH CENTRUM UTRECHT No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2024-03-08

Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:

ERC-2023-COG: ERC CONSOLIDATOR GRANTS

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UMC UTRECHT

2.00M€ | Lider

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Duración del proyecto: 70 meses Fecha Inicio: 2024-03-08
Fecha Fin: 2030-01-31

Líder del proyecto

UNIVERSITAIR MEDISCH CENTRUM UTRECHT

TRL 4-5

Presupuesto del proyecto 2M€

Descripción del proyecto 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.

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