Designer RNA stalls hepatitis in mice

From Boston, at a conference on Retroviruses and Opportunistic Infections

Using strips of synthetic RNA that interfere with normal gene action, scientists working with mice have stopped the progression of hepatitis, a lethal inflammation of the liver often caused by a virus. The study is the first to show that this technique, called RNA interference, can improve the health of a mammal.

RNA is the genetic material that serves as a template for protein production by cells. The body sometimes sabotages its RNA as a way to dispose of a cell that has been infiltrated by viruses that have genes consisting of RNA rather than DNA. Earlier test-tube studies suggested that RNA molecules could silence viral genes, as well as some genes associated with cancer. Some research further indicated that RNA interference could halt the proliferation of viruses in lab dishes (SN: 8/10/02, p. 93: Lab tool may spawn new antiviral drugs; 9/21/02, p. 189: RNA interferes with cancer-cell growth).

In the new study, Judy Lieberman of Harvard Medical School in Boston and her coworkers used mice with a form of hepatitis that is exacerbated by an inflammatory protein called Fas. Most such mice die within 3 days.

But when the scientists synthesized RNA designed to inactivate the gene encoding Fas, more than 80 percent of mice treated during a 10-day test period survived. The interfering RNA accumulated in the liver, the researchers found.

Deactivating a specific gene with synthetic RNA offers hope that this approach will work against pathogenic viruses, including the AIDS virus, says Mario Stevenson of the University of Massachusetts in Worcester.

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