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- W1963516279 abstract "A number of groups have published reports of antiviral efficacy associated with the delivery of siRNA directed against the influenza virus using either lipoplex or polyplex mediated siRNA delivery. In order to assess the extent to which the immunostimulatory properties of siRNA may have contributed to these results we developed non- immunostimulatory analogues of the previously published NP1496 and PA2087 siRNA. siRNA were prepared containing minimal chemical modifications previously shown to abrogate immune stimulation while retaining the ability to mediate RNAi. The immunostimulatory properties of all siRNA were confirmed by intravenous injection of liposome encapsulated siRNA followed by determination of interferon alpha in the plasma 6h post-injection in mice. When tested in an in vitro cell-based system the modified, non-stimulatory siRNA potently inhibited influenza virus replication in MDCK cells. However, the modified siRNA lost all previously observed antiviral efficacy when delivered to mice infected with Influenza A/PR/8/34. Mice were treated either intranasally using lipoplex (Oligofectamine TM) at 1 mg/kg, intranasally as ‘naked’ siRNA at 12.5 mg/kg or by intravenous administration as PEI polyplex at 6 mg/kg. This was in contrast to previously reported studies yielding substantial antiviral efficacy when using the immunostimulatory parent molecules. When these studies were repeated using the immunostimulatory parent molecules we observed a significant reduction in viral titre in the mouse lung as measured by HA EIA. The results suggest caution when interpreting results obtained in vivo using immunostimulatory siRNA, in particular within the context of anti-viral applications." @default.
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- W1963516279 date "2006-01-01" @default.
- W1963516279 modified "2023-10-08" @default.
- W1963516279 title "798. Anti-Influenza-Viral Efficacy Attributed to siRNA Formulated as Simple Lipoplex or PEI Polyplexes Is a Result of Their Immunostimulatory Properties" @default.
- W1963516279 doi "https://doi.org/10.1016/j.ymthe.2006.08.887" @default.
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