Comparative Evaluation of Target-Specific GFP Gene Silencing Efficiencies for Antisense ODN,Synthetic siRNA,and siRNA Plasmid Complexed with PEI-PEG-FOL Conjugate

摘要

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 poly-electrolyte 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 ￡ 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.