Department of Biological Sciences and Graduate School of Nanoscience and Technology, Korea Advanced Institute of Science and Technology, Daejeon 305-701, South Korea.
J Control Release. 2010 Jun 15;144(3):306-13. doi: 10.1016/j.jconrel.2010.03.002. Epub 2010 Mar 4.
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 cleavable disulfide and noncleavable thioether linkages to evaluate their gene silencing efficiencies upon complexation with Lipofectamine2000. The PEGylation site at the four siRNA termini and PEG molecular weight were not critical factors 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 without showing a target sequence-specific manner. 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.
小干扰 RNA（siRNA）通过可裂解的二硫键和不可裂解的硫醚键与聚乙二醇（PEG）在四个不同的末端（正义 3'、正义 5'、反义 3'和反义 5'）连接，以评估它们与 Lipofectamine2000 复合时的基因沉默效率。PEG 在 siRNA 四个末端的连接位置和 PEG 分子量并不是影响基因沉默活性的关键因素。可裂解的 siRNA-PEG 缀合物与裸 siRNA 具有相当的基因沉默活性，并表现出对靶 mRNA 的序列特异性降解。有趣的是，不可裂解的 siRNA-PEG 缀合物可被 Dicer 加工，从而发挥 RNAi 效应，而不表现出靶序列特异性。然而，只有可裂解的 siRNA-PEG 缀合物与不可裂解的 siRNA-PEG 缀合物相比，显著降低了 INF-α释放的程度，这表明它们可潜在地用于治疗性 siRNA 应用。
