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. 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.