Effective mRNA Inhibition in PANC-1 Cells in Vitro Mediated via an mPEG–SeSe–PEI Delivery System

Abstract

RNA interference (RNAi)-mediated gene therapy is a promising approach to cure various diseases. However, developing an effective, safe, specific RNAi delivery system remains a major challenge. In this study, a novel redox-responsive polyetherimide (PEI)-based nanovector, mPEG–SeSe–PEI, was developed and its efficacy evaluated. We prepared three mPEG–SeSe–PEI vector candidates for small interfering glyceraldehyde-3-phosphate dehydrogenase (siGADPH) and determined their physiochemical properties and transfection efficiency using flow cytometry and PEG_11.6–SeSe–PEI polymer. We investigated the silencing efficacy of GADPH mRNA expression in PANC-1 cells and observed that PEG_11.6–SeSe–PEI/siGADPH (N/P ratio=10) polyplexes possessed the appropriate size and zeta-potential and exhibited excellent in vitro gene silencing effects with the least cytotoxicity in PANC-1 cells. In conclusion, we present PEG_11.6–SeSe–PEI as a potential therapeutic gene delivery system for small interfering RNA (siRNA).

Graphical Abstract