Non-Covalent Tagging of siRNA Oligonucleotides with Short Block Copolymer Sequences for Improved Targeted Delivery
Description: The TANGO project aims at introducing a new approach to improve the in vivo delivery of oligonucleotides like small interfering RNA (siRNA) which hold great promise for the targeted gene silencing in several diseases. The idea is to form non-covalent siRNA-PEG conjugates by complexing siRNA molecules with chitosan-block-PEG copolymer chains. Compared to common polyplexes, lipoplexes or polyion complex micelles, the novelty consists in using small blocks of positively charged chitosan in order to form soluble monomolecular complexes featuring a single siRNA molecule per conjugate. The method combines the efficiency of the PEGylation with the ease and reversibility of the electrostatic complexation. The ultimate goal is to obtain stable conjugates through the simple mixing of siRNA, copolymer and ligand in solution. The biological potential of non-covalent siRNA-PEG conjugates functionalized with mannose or a monoclonal antibody will be investigated in vitro and in vivo in the context of the rheumatoid arthritis.
Partners: Laboratoire Ingénierie des Matériaux Polymères (Lyon), Institut Galien Paris-Sud (Chatenay Malabry)