Cationic lipid nanoemulsions for RNAi screening

J. Bruniaux, E. Sulpice, F. Mittler, I. Texier, X. Gidrol, F.P. Navarro

Keywords: siRNA, lipid nanoparticles, transfection, gene delivery, RNAi screening


Since the discovery of RNA interference, many efforts have been made to broaden perspectives of small interfering RNA (siRNA) in research and clinical work. siRNA shows a specific and effective gene silencing activity through a sequence specific down-regulation of the complementary messenger RNA. However, the siRNA-mediated gene knock down requires that siRNA can reach the protein complex RISC in the cytoplasm. To deliver them acrros plasma membrane, transfection agents have been designed, especially cationic compounds. Here, we have manufactured lipid nanoemulsions entrapping lipophilic cyanine derivatives for fluorescence monitoring and incorporating cationic compounds for carrying siRNA. Using this multifunctional particle-based transfection agent, we have demonstrated that particles 1) are relatively well tolerated by cells, 2) enable an efficient complexation and retention of siRNA and 3) allow the down regulation of green fluorescent protein in cell model. Next steps will include the improvement of transfection efficiency and the surface functionalization of particles with specific ligand in order to target cells hard to transfect using commercially available agents.