1. Gene therapeutic approach for inhibiting hepatitis C virus replication using a recombinant protein that controls interferon expression.
- Author
-
Joo CH, Lee U, Nam YR, Jung JU, Lee H, Cho YK, and Kim YK
- Subjects
- Adenoviridae genetics, Cell Line, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Genetic Vectors genetics, HeLa Cells, Hepatitis C virology, Humans, Immunoblotting, Models, Biological, Recombinant Proteins genetics, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Regulation, Genetic Therapy methods, Hepacivirus metabolism, Hepatitis C therapy, Interferons metabolism, Recombinant Proteins metabolism, Virus Replication genetics
- Abstract
The hepatitis C virus (HCV) is a continuing threat to public health. The systemic administration of interferon alpha with ribavirin is the only currently approved treatment. However, this treatment is associated with a wide spectrum of systemic side effects that limits its effectiveness; thus, there is an urgent need for new treatment modalities. In this study, we describe a novel anti-HCV strategy employing a recombinant transcription factor that we have engineered in such a way that NS3/4a viral protease controls its intracellular localization, thereby restoring interferon secretion specifically in cells infected with HCV. Proof-of-concept experiments validated the strategy, showing that the recombinant transcription factor was triggered to stimulate interferon promoter by NS3/4A and remained inactive in cells without NS3/4a. Using an adenovirus-associated viral vector delivery system, we found that the recombinant transcription factor inhibited HCV replication effectively in vitro in cultured cells.
- Published
- 2010
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