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H2020Individual fellowship2020–2022

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

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2020-05-14 → 2022-05-25
EU contribution
€212,934
Participants
1
Scheme
MSCA-IF-EF-SE

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Results in brief

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

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. However, to propel these structures towards clinical applications, challenges such as poor nuclease resistance, biodistribution and cellular delivery need to be addressed. An important first step is to understand how they interact with biological components. In particular, upon injection, it is known that serum proteins bind to nanoparticles. The composition of this so-called protein-corona on RNA particles remains fully unexplored. Yet, the protein corona has been shown to dramatically influence biological outcomes of other types of nanoparticles (toxicity, or cellular uptake). Herein, we propose to characterise the protein corona on RNA nanoparticles, as well as understand the role of the corona on the fate of RNA structures. Overall, the project aims at providing tools and rules for rational engineering of the protein corona on RNA nanoparticles. The project also aims at improving fundamental understanding on nanoparticles for drug delivery.

Data: CORDIS, © European Union

Project 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.

Original text from CORDIS.

Participants

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Data: CORDIS, © European Union