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        A Hepatitis C Virus Xenograft Mouse Efficacy Model

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        1026
        The lack of a robust small-animal model for hepatitis C virus (HCV) has hindered the discovery and development of novel drug treatments for HCV infections. We developed a reproducible and easily accessible xenograft mouse efficacy model in which HCV RNA replication is accurately monitored in vivo by real-time, noninvasive, whole-body imaging of γ-irradiated SCID mice implanted with a mouse-adapted luciferase replicon-containing Huh-7 cell line. The model has been validated by demonstrating that both a small molecule NS3/4A protease inhibitor (BILN 2061) and human interferon- α (IFN-α) decreased HCV RNA replication and that treatment withdrawal resulted in a rebound in replication, which paralleled clinical outcomes in humans. The efficacy of protease inhibitor plus IFN-α demonstrated the application of the model for testing compounds in combination therapies. This robust mouse efficacy model provides a powerful tool for rapid evaluation of potential anti-HCV compounds in vivo.
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