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Small interfering RNAs (siRNAs) appear to silence genes in mice without triggering an immune response, according to researchers at the California Institute of Technology in Pasadena. Mark Davis and colleagues gave mice naked synthetic siRNAs against fatty acid synthase (FAS), c-MYC, or luciferase, through intraperitoneal injections or via the tail vein using either low-pressure (1% volume/weight) or high-pressure (10% volume/weight) methods.
Enzyme-linked immunosorbent assay (ELISA) showed that siRNA failed to trigger a strong type I interferon alpha response regardless of the siRNA or type of injection method. In comparison, polyinosinic acid:polycytidylic acid – poly(I:C), a long, double-stranded RNA analog – triggered strong interferon responses. The researchers also looked for effects mediated by Toll-like receptors 3 and 9, which are thought to recognize siRNA and trigger interferon upregulation. ELISA analysis showed that while poly(I:C) triggered a strong interleukin-12 response, the siRNAs did not.
High-pressure tail-vein injection of siRNA...