targeting the highly conserved core region of the HCV genome and the plasmid pGL3-attB-CoreFluc, which encoded the fly luciferase fusing to the downstream of HCV core protein as a silencing target, were cotransfected into Huh7 cells and the mouse liver. In cell culture, all the three shRNAs caused significant reduction in the level of HCV core protein while the sramble shRNA had no inhibitory effect on core protein expression. This observation had been previously reported by other groups. But Suzuki et al considered that shRNA452 construct mediated more effective inhibition of HCV replication than the other core-shRNAs. In our test, the inhibitory effects of these three shRNAs had no statistic difference. It was also found that the loss of Fluc activity coincided with the degradation of HCV core protein, which indicated that the Fluc activity could reflect the expression level of core protein successfully. In the transient mouse model, the inhibitory effect of shRNA452 and shRNA523 was examined by real-time bioluminescence imaging. The effect of shRNA-523 was detectable as early as 24 h after transfection and became even more pronounced at later time points. The effect of shRNA-452 was not detected until 48 h post-transduction. There are some special requirements for assays used in drug discovery that are related to the nature of the information needed to understand drug action. Besides, advanced characterization of compounds typically requires answers to questions such as the relationship between duration of action and pharmacokinetics or the maintenance of efficacy after Sunset Yellow FCF repeated dosing. So a stable mouse model can help to identify and evaluate specific compounds for their potential efficacy. Phage WC31 integrase has emerged as a potent tool for achieving long-term gene expression in different tissues. Several studies document that phage WC31 integrase can site-specifically integrate plasmid DNA bearing an attB site into endogenous positions in the genome of mouse liver cells. Using WC31 integrase, long-term expression of Core-Fluc was GW9662 distributor achieved. However, final expression values attained were substantially lower than the initial values at day 1 post-transfection. This is consistent with the findings of other groups and represents a transition from initial high levels of expression arising from unintegrated pDNA to steady-state expression levels resulting from integrated pDNA. In this stable mouse model, the inhibitory effect of shRNA523 was examined, and significant reduction in Fluc activity was observed. The inhibitory effect persisted for 1 day after a single injection. Short hairpin RNAs have emerged as a novel therapeutic modality, but there is increasing concern over nonspecific effects in vivo. Here, physiological effects of hydrodynamic inj