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Scientists use gene silencing to block hepatitis C virus in mice
  

 

One of the body's important surveillance mechanisms that is of great interest in basic genomics research may be therapeutically useful for treating hepatitis C infections—at least in mice. Known as RNA interference (RNAi), the mechanism can silence genes by interfering with the production of proteins.

Several recent studies have shown that RNAi can inhibit HIV and poliovirus in cell cultures, at least temporarily. The mouse study is one of the first to demonstrate that the mechanism can be effective in adult mammals.


RNA interference in adult mice. View full

In a recent issue of Nature, Mark A. Kay, of Stanford University School of Medicine in California, and colleagues report that RNAi can interfere with the expression of human hepatitis C virus that has been inserted into mice. In human beings, hepatitis C virus infection is a serious medical problem worldwide and the most common reason for liver transplantation in the United States and Europe. (Hepatitis C is an RNA virus.)

To demonstrate the therapeutic potential of RNAi, the researchers used 'small interfering RNAs' (siRNAs) to mimic intermediates in the RNAi pathway. In the mouse cells, the siRNAs triggered a defense mechanism that degraded part of the hepatitis C genome.

"We're interested in seeing if RNAi could be used to treat hepatitis C or one of the other important human pathogens," says Kay. "This is an encouraging first step, but much more work needs to be done to see how fruitful this application is going to be."

That work will include figuring out effective methods of delivering therapeutic RNAs to cells. The delivery mechanism used by Kay's team was DNA templates that expressed in vivo short, interfering RNA molecules in the shape of hairpins (shRNAs). "These findings indicate that plasmid-encoded shRNAs can induce a potent and specific RNAi response in adult mice," they write in Nature.

Whether or not RNAi becomes the basis for new therapies, the method will change how researchers study the functions of genes and investigate potential drug targets. According to Kay's group, RNAi is a more promising system than genetically altered mice because groups of genes can be simultaneously turned off without the time-consuming process of crossing 'knockout' mice.

See related GNN articles
»Silencing Genes in HIV
»Scientists shut down genes in poliovirus, HIV in cell cultures

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McCaffrey, A.P. et al. Gene expression: RNA interference in adult mice. Nature 418, 38-39 (July 4, 2002).
 

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