Selection and adaptation of siRNA vectors by live cells – SACSI

The SACSI project will study the self-assembly of unprecedented pH-responsive – undergoing conformational changes upon cell uptake that promote endosomal escape siRNA release in the cytoplasm – amphiphilic dynamic covalent polymers for generating targeted nano-vectors of siRNA capable of adaptation on 2 different scales: i) following siRNA recognition and complexation, and ii) throughout the penetration through cell membranes. The proposed methodology combines a cell-based functional screening which exploits the templating effect whereby siRNA triggers the formation of its own vector, with a cutting-edge mass spectrometry technique to enable the identification and quantification of the selected nano-vectors that have been transported inside cells. The ambition of this project is to discover self-fabricated multi-component siRNA vectors that adapt throughout the different steps of the delivery process in order to maximize its efficacy.