Hepatic toll-like receptors can be activated by application of siRNAs in vivo via MyD88-dependent pathways which can be controlled by chemical ribose modifications of the siRNA ba…
CI Real, R Bröring, M John, K Jahn-Hofmann, L Ickenstein, K Kleinehr, G Gerken, JF Schlaak · Zeitschrift für Gastroenterologie · 2012 · Heft 01
Bibliografische Angaben
Zusammenfassung
Introduction: siRNAs are being developed for the therapeutic use in liver cancer, viral hepatitis, metabolic disorders and others. We have previously shown that chemical modifications of siRNAs suppress immunologically mediated off-target effects in vitro and in vivo. Here, we assessed efficacy and the Toll-like receptor dependent immune-stimulatory effects of differently modified siRNAs in vivo. Methods: Nanolipid-formulated (LNP01) siRNAs preferentially targeting hepatocytes were injected into C57Bl/6, TLR3-/- and MyD88-/- mice. After 6h and 48h tissue (liver, heart, spleen, kidney) and blood were prepared and…
