RNA interference blocks gene expression and RNA synthesis from hepatitis C replicons propagated in human liver cells.

نویسندگان

  • Joyce A Wilson
  • Sumedha Jayasena
  • Anastasia Khvorova
  • Sarah Sabatinos
  • Ian Gaël Rodrigue-Gervais
  • Sudha Arya
  • Farida Sarangi
  • Marees Harris-Brandts
  • Sylvie Beaulieu
  • Christopher D Richardson
چکیده

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.

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عنوان ژورنال:
  • Proceedings of the National Academy of Sciences of the United States of America

دوره 100 5  شماره 

صفحات  -

تاریخ انتشار 2003