The non-specific activation of liver tissue by siRNAs in vivo can be controlled by chemical ribose modifications of siRNAs

Introduction: siRNAs have been developed for therapeutic use in liver cancer, viral hepatitis or metabolic disorders. We previously showed that chemical modification of siRNAs control immunologically mediated off-target effects in isolated liver cells in vitro. In the present study, we assessed efficacy and immune-stimulatory effects of these siRNAs in vivo. Methods: Human and murine hepatocytes and non-parenchymal liver cells were transfected with siRNAs against APOB1 (APO), interferon-sensitive gene15 (ISG15) or control siRNAs against luciferase (LUC) or galactosidase (GAL). For in vivo use, siRNAs were formul…