The activation of the hepatic innate immune system by siRNA is controlled by chemical modifications and may involve endosomal Toll-like receptors

Aims: siRNAs are being developed for the therapeutic use in liver cancer, viral hepatitis or metabolic disorders. Undesired immune stimulation of siRNA are usually studied in human cell lines or PBMC. Here, we assessed the capacity of chemically modified versus unmodified siRNAs to trigger immune responses in primary human cells of the liver. Methods: siRNAs targeting APOB1 (APO, APO-chol) and control siRNAs targeting luciferase (LUC) or galactosidase (GAL) mRNA were transfected into primary isolated human cells (PBMC, Kupffer cells, hepatocytes). Human hepatoma cells (Huh7) were used for comparison. Expression…