In vivo knockdown, mediated by LNP01-formulated siRNAs, of HCV pro-viral factor ISG15 increased responsiveness to Interferon

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). ISG15 has been identified as pro-viral host factor promoting HCV replication. Therefore, hepatocyte-specific suppression of ISG15 expression may be a promising approach to overcome non-response to standard combination treatment of HCV patients and may lead to new therapeutic concepts in the future. Methods: Nanolipid-formulated (LNP01) siRNAs preferentially targeting the liver were injected into C57Bl/6 mice. After different time points (6h, 24…