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Design of polymer brushes vectors for RNA delivery

In the last decade, delivery of therapeutic RNA has achieved tremendous progress in both gene therapy and vaccine development. Typically, transfection of sufficient and intact RNA payload into cells relies on its proper association with delivery vectors. Particularly, cationic polymer brushes of unique high grafting density have displayed effective RNA uptake and stabilization enabling to retain high transfection and knock down efficiencies over prolonged periods of time, however, these polyplexes tend to dissociate relatively fast in complex physiological conditions, limiting their translation into clinical applications. Recently, characterization of the cytoplasmic interactome revealed that the primary mechanism for such polyplex destabilization is the competitive binding of the cytosolic biomolecules. Therefore, we propose to study a library of brush chemistries, architectures and associated physico-chemical behavior and biophysical interactions in order to modulate the polymer vector interactome controlling polyplex complexation, RNA release and protein expression. 

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