In vivo treatment with nanolipid-formulated siRNAs targeting ISG15 leads to enhanced responsiveness to interferon in primary hepatocytes
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: Non-response of HCV patients to combination therapy has previously been associated with a strong up-regulation of the interferon stimulated gene 15 (ISG15). The ISG15 gene product is a pro-viral factor for HCV replication in hepatocytes, but not in non-parenchymal liver cells (NPC). RNAi-based suppression of ISG15 expression in hepatocytes may overcome non-response to standard combination treatment. Methods: Different Nanolipid-formulated (LNP01) siRNAs, preferentially targeting hepatocytes, were injected into C57Bl/6 mice. After 6h, 48h and 10d tissue (liver, heart, spleen, kidney) and blood were…