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Engineering the protein corona on RNA nanoparticles for improved nucleic acids-based therapies delivery

Project description

Improving nanoparticle-based drug delivery

Recent advances in nanotechnology have paved the way for the use of nanoparticles in cancer therapy as drug delivery vehicles. Despite the advantages of nanoparticle drug delivery, including high selectivity and reduced toxicity, there are various aspects to the process that remain elusive, such as the acquisition of proteins upon in vivo injection. The EU-funded NanoRNA_PC project will employ state-of-the-art methodologies to characterise the protein corona formed on RNA nanoparticles upon interaction with biological components. Understanding the composition of the protein corona on nanoparticles is expected to improve their design as well as their biological outcome.

Objective

In the past three decades, nanomedicine has emerged as a promising strategy in cancer treatment and has led to numerous proposed drug delivery systems. Nanoparticles aim to improve selectivity towards cancer cells while reducing off-target effects and toxicity towards normal cells. Among these systems, self-assembled RNA nanoparticles have been of great interest for drug delivery, because of their low cost, high yielding assembly and retained functionality. Yet, challenges such as poor nuclease resistance, biodistribution and cellular delivery remains to be addressed, to fully propels these structures towards clinical applications. To optimize these systems, there is a huge need to understand precisely their interactions with biological components. In particular, upon injection in vivo, it is known that serum proteins adsorb on nanoparticles. The composition of this so-called protein-corona on RNA particles remains fully unexplored.

Herein, I propose to characterize the protein corona on RNA nanoparticles using state-of-the-art methodologies (proteomics, super-resolution microscopy, SELEX), as well as understand the role the corona on the fate of RNA structures. I will engineer the protein corona to improve biological outcomes of RNA particles, previously developed by Sixfold Bioscience Ltd. Overall, the project aims at providing tools and rules for rational engineering of the protein corona. In the long term, the project, grouping experts in industry and in academia, aims towards the development of a preclinical candidate, as well as answering fundamental questions on nanoparticles delivery.

Coordinator

SIXFOLD BIOSCIENCE LTD
Net EU contribution
€ 212 933,76
Address
THE IMPERIAL COLLEGE WHITE CITY INC INNOVATION HUB
W12 0BZ London
United Kingdom

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SME

The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed.

Yes
Region
London Inner London — West Kensington & Chelsea and Hammersmith & Fulham
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Links
Total cost
€ 212 933,76