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Overcoming cellular barriers to therapeutic RNA delivery using extracellular ves...

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 di... ver más

31/01/2025

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

Ver 2 Participantes

Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2020-01-14

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

ERC-2019-STG: ERC Starting Grant

I+D

Cerrada hace 6 años

0% 100%

2 Participantes

UMC UTRECHT

1.50M€ | Lider

EMILIO ESTEBAN

334.27K€ | Participante

Últimas noticias

29-11-2024: IDAE En las últimas 48 horas el Organismo IDAE ha otorgado 4 concesiones

29-11-2024: ECE En las últimas 48 horas el Organismo ECE ha otorgado 2 concesiones

29-11-2024: CMVAMADRID En las últimas 48 horas el Organismo CMVAMADRID ha otorgado 37 concesiones

Duración del proyecto: 60 meses Fecha Inicio: 2020-01-14
Fecha Fin: 2025-01-31

Líder del proyecto

UNIVERSITAIR MEDISCH CENTRUM UTRECHT

TRL 4-5

Presupuesto del proyecto 2M€

Descripción del proyecto 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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