RNA interference blocks gene expression and RNA synthesis from hepatitis C replicons propagated in human liver cells
| Autor: | Ian Gaël Rodrigue-Gervais, Sudha Arya, Joyce A. Wilson, Anastasia Khvorova, Farida Sarangi, Sylvie Beaulieu, Christopher D. Richardson, Marees Harris-Brandts, Sarah A. Sabatinos, Sumedha D. Jayasena |
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| Jazyk: | angličtina |
| Rok vydání: | 2003 |
| Předmět: |
Small interfering RNA
Time Factors Transcription Genetic Trans-acting siRNA Blotting Western Genetic Vectors RNA-dependent RNA polymerase Biology Transfection Virus Replication Cell Line Small hairpin RNA DNA-directed RNA interference Tumor Cells Cultured Humans RNA Messenger RNA Small Interfering Multidisciplinary Models Genetic RNA Antibodies Monoclonal Biological Sciences Blotting Northern Virology Molecular biology Hepatitis C digestive system diseases Antisense RNA RNA silencing Electroporation Liver Mutation RNA Viral Electrophoresis Polyacrylamide Gel RNA Interference Plasmids |
| Popis: | RNA interference represents an exciting new technology that could have therapeutic applications for the treatment of viral infections. Hepatitis C virus (HCV) is a major cause of chronic liver disease and affects >270 million individuals worldwide. The HCV genome is a single-stranded RNA that functions as both a messenger RNA and replication template, making it an attractive target for the study of RNA interference. Double-stranded small interfering RNA (siRNA) molecules designed to target the HCV genome were introduced through electroporation into a human hepatoma cell line (Huh-7) that contained an HCV subgenomic replicon. Two siRNAs dramatically reduced virus-specific protein expression and RNA synthesis to levels that were 90% less than those seen in cells treated with negative control siRNAs. These same siRNAs protected naive Huh-7 cells from challenge with HCV replicon RNA. Treatment of cells with synthetic siRNA was effective >72 h, but the duration of RNA interference could be extended beyond 3 weeks through stable expression of complementary strands of the interfering RNA by using a bicistronic expression vector. These results suggest that a gene-therapeutic approach with siRNA could ultimately be used to treat HCV. |
| Databáze: | OpenAIRE |
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