Effects of PEG anchors in PEGylated siRNA lipoplexes on in  vitro gene‑silencing effects and siRNA biodistribution in mice.

Effects of PEG anchors in PEGylated siRNA lipoplexes on in vitro gene‑silencing effects and siRNA biodistribution in mice. Mol Med Rep. 2020 Nov;22(5):4183-4196 Authors: Hattori Y, Tamaki K, Sakasai S, Ozaki KI, Onishi H Abstract Polyethylene glycol (PEG)‑modifications (PEGylations) of cationic liposome/small interfering RNA complexes (siRNA lipoplexes) can enhance their systemic stability. The present study determined the effects of PEG anchors in PEGylated siRNA lipoplexes on in vitro gene‑silencing effects and siRNA biodistribution after intravenous injection. Three types of dialkyl or trialkyl cationic lipids were used in the current study for the preparation of cationic liposomes. Additionally, various PEGylated siRNA lipoplexes that contained PEG‑1,2‑distearoyl‑sn‑-glycero‑-3‑phosphoethanolamine (DSPE), PEG‑1,2‑distearoyl‑rac‑glycero‑3‑-methylpolyoxyethylene (DSG), PEG‑cholesterol (PEG‑Chol) and PEG‑chondroitin sulfate conjugate (PEG‑CS) were prepared. The results revealed that PEGylation of siRNA lipoplexes with PEG‑DSPE strongly decreased gene‑silencing effects in cells. In contrast, those with PEG‑DSG, PEG‑Chol and PEG‑CS did not largely decrease gene-silencing effects. However, regardless of the PEG‑derivative type, PEGylation of siRNA lipoplexes decreased their agglutination with erythrocytes. Furthermore, intravenous injection of PEGylated siRNA lipoplexes markedly decre...
Source: Molecular Medicine Reports - Category: Molecular Biology Tags: Mol Med Rep Source Type: research