| Autor: |
Zhu Q; Department of Pharmacology, Novartis Vaccines and Diagnostics, Chiron Corportion, Emeryville, CA 94608. Qing_zhu@chiron.com, Oei Y, Mendel DB, Garrett EN, Patawaran MB, Hollenbach PW, Aukerman SL, Weiner AJ |
| Jazyk: |
angličtina |
| Zdroj: |
Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2006 Oct; Vol. 50 (10), pp. 3260-8. |
| DOI: |
10.1128/AAC.00413-06 |
| Abstrakt: |
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 gamma-irradiated SCID mice implanted with a mouse-adapted luciferase replicon-containing Huh-7 cell line (T7-11). The model was validated by demonstrating that both a small-molecule NS3/4A protease inhibitor (BILN 2061) and human alpha interferon (IFN-alpha) decreased HCV RNA replication and that treatment withdrawal resulted in a rebound in replication, which paralleled clinical outcomes in humans. We further showed that protease inhibitor and IFN-alpha combination therapy was more effective in reducing HCV RNA replication than treatment with each compound alone and supports testing in humans. This robust mouse efficacy model provides a powerful tool for rapid evaluation of potential anti-HCV compounds in vivo as part of aggressive drug discovery efforts. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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