Comparative evaluation of target-specific GFP gene silencing efficiencies for antisense ODN, synthetic siRNA, and siRNA plasmid complexed with PEI-PEG-FOL conjugate.

Cell specific gene silencing effects of antisense oligodeoxynucleotide (AS-ODN), synthetic small interfering RNA (siRNA-S), and siRNA expressing plasmid (siRNA-P) were comparatively evaluated. Poly(ethylenimine) (PEI) and PEI-graft-poly(ethylene glycol)-folate (PEI-PEG-FOL) conjugate were used to form nanosized polyelectrolyte complexes with the above three nucleic acids coding for inhibition of green fluorescent protein (GFP) expression. The three nucleic acid complexes formulated with either PEI or PEI-PEG-FOL had comparable sizes and surface zeta potential values. Among the three inhibitory nucleic acids, siRNA-S, when complexed with PEI-PEG-FOL, exhibited the most dose-effective and fastest gene silencing effect for FOL receptor overexpressing KB cells, because the siRNA-S could be directly delivered, via FOL receptor-mediated endocytosis, into the cytoplasm compartment where the degradation processing of target GFP mRNA occurred in a sequence-specific manner.