Conjugation of siRNA with Comb‐Type PEG Enhances Serum Stability and Gene Silencing Efficiency

Abstract

A thiol-modified siRNA targeting the enhanced green fluorescence protein (eGFP) gene was conjugated with RAFT-synthesized, pyridyl disulfide-functional poly(PEG methyl ether acrylate)s (p(PEGA)s). siRNA-p(PEGA) conjugates demonstrated significantly enhanced in vitro serum stability and nuclease resistance compared to the unmodified and thiol-modified siRNA. The complexes of siRNA-p(PEGA) conjugates with a fusogenic peptide, KALA ((+)/(-) = 2) inhibited the protein expression approximately 28-fold more than the KALA complex of the unmodified siRNA. The protein inhibition caused by siRNA-p(PEGA)-KALA complexes (56 ± 5%-58 ± 3% of the fluorescence expressed in non-treated cells) was comparable to the effect of the unmodified siRNA-lipofectamine complex (77 ± 7%).