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RNA interference blocks gene expression and RNA synthesis from hepatitis C replicons propagated in human liver cells.
Wilson, Joyce A; Jayasena, Sumedha; Khvorova, Anastasia; Sabatinos, Sarah; Rodrigue-Gervais, Ian Gaël; Arya, Sudha; Sarangi, Farida; Harris-Brandts, Marees; Beaulieu, Sylvie; Richardson, Christopher D.
Afiliação
  • Wilson JA; Ontario Cancer Institute, 620 University Avenue, Suite 706, Toronto, ON, Canada M5G 2C1.
Proc Natl Acad Sci U S A ; 100(5): 2783-8, 2003 Mar 04.
Article em En | MEDLINE | ID: mdl-12594341
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Replicação Viral / RNA / RNA Viral / Hepatite C / RNA Interferente Pequeno / Interferência de RNA / Fígado Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2003 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Replicação Viral / RNA / RNA Viral / Hepatite C / RNA Interferente Pequeno / Interferência de RNA / Fígado Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2003 Tipo de documento: Article