Gene silencing efficiency of siRNA-PEG conjugates

Abstract

Small interfering RNA (siRNA) was conjugated with poly(ethylene glycol) (PEG) at four different terminal ends (sense 3’, sense 5’, antisense 3’, and antisense 5’) via a cleavable disulfide and a noncleavable thioether linkage to evaluate their gene silencing efficiencies upon complexation with $Lipofectamine^{TM}$2000. The PEGylation site at the four siRNA termini and PEG molecular weight were not a critical factor to significantly affect gene silencing activities. Cleavable siRNA-PEG conjugates showed comparable gene silencing activities to naked siRNA, and exhibited sequence-specific degradation of a target mRNA. Interestingly, noncleavable siRNA-PEG conjugates were processed by Dicer, enabling to exert RNAi effect with demonstrating non-specific mRNA degradation. However, only cleavable siRNA-PEG conjugates significantly reduced the extent of $INF-\alpha$ release as compared to noncleavable siRNA-PEG conjugates, suggesting that they can be potentially used for therapeutic siRNA applications.