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RNA interference blocks gene expression and RNA synthesis from hepatitis C replicons propagated in human liver cells.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2003 Mar 04; Vol. 100 (5), pp. 2783-8. Date of Electronic Publication: 2003 Feb 19. - Publication Year :
- 2003
-
Abstract
- 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.
- Subjects :
- Antibodies, Monoclonal metabolism
Blotting, Northern
Blotting, Western
Cell Line
Electrophoresis, Polyacrylamide Gel
Electroporation
Genetic Vectors
Humans
Models, Genetic
Mutation
Plasmids metabolism
RNA, Messenger metabolism
Time Factors
Transcription, Genetic
Transfection
Tumor Cells, Cultured
Virus Replication genetics
Hepatitis C metabolism
Liver cytology
RNA metabolism
RNA Interference
RNA, Small Interfering physiology
RNA, Viral genetics
Virus Replication physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0027-8424
- Volume :
- 100
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 12594341
- Full Text :
- https://doi.org/10.1073/pnas.252758799