Inhibition of hepatitis B virus in mice by RNA interference

Anton P. McCaffrey, Hiroyuki Nakai, Kusum Pandey, Zan Huang, Felix H. Salazar, Hui Xu, Stefan F. Wieland, Patricia L. Marion, Mark A. Kay

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Abstract

Hepatitis B virus (HBV) infection substantially increases the risk of chronic liver disease and hepatocellular carcinoma in humans. RNA interference (RNAi) of virus-specific genes has emerged as a potential antiviral mechanism. Here we show that RNAi can be applied to inhibit production of HBV replicative intermediates in cell culture and in immunocompetent and immunodeficient mice transfected with an HBV plasmid. Cotransfection with plasmids expressing short hairpin RNAs (shRNAs) homologous to HBV mRNAs induced an RNAi response. Northern and Southern analyses of mouse liver RNA and DNA showed substantially reduced levels of HBV RNAs and replicated HBV genomes upon RNAi treatment. Secreted HBV surface antigen (HBsAg) was reduced by 94.2% in cell culture and 84.5% in mouse serum, whereas immunohistochemical detection of HBV core antigen (HBcAg) revealed >99% reduction in stained hepatocytes upon RNAi treatment. Thus, RNAi effectively inhibited replication initiation in cultured cells and mammalian liver, showing that such an approach could be useful in the treatment of viral diseases.

Original languageEnglish (US)
Pages (from-to)639-644
Number of pages6
JournalNature Biotechnology
Volume21
Issue number6
DOIs
Publication statusPublished - Jun 1 2003
Externally publishedYes

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ASJC Scopus subject areas

  • Microbiology

Cite this

McCaffrey, A. P., Nakai, H., Pandey, K., Huang, Z., Salazar, F. H., Xu, H., ... Kay, M. A. (2003). Inhibition of hepatitis B virus in mice by RNA interference. Nature Biotechnology, 21(6), 639-644. https://doi.org/10.1038/nbt824