Virus versus virus

Harmless delivery treats hepatitis B

SAN FRANCISCO — By fine-tuning the genetic code in a snippet of RNA, researchers thwarted the hepatitis B virus in mice without causing apparent toxicity.

When delivered into the liver by a different, harmless virus, the customized RNA blocked more than 95 percent of the production of an enzyme that the hepatitis B virus needs to replicate. The treatment effectively halted the proliferation of the disease-causing virus, according to an unpublished study presented June 10 in San Francisco at the Beyond Genome conference.

“If you drop the viral [count] to a low enough level, the body might be able to clear it,” says lead scientist Anton McCaffrey, an RNA biochemist at the University of Iowa in Iowa City. About 400 million people worldwide have chronic hepatitis B infections, which can lead to life-threatening cirrhosis and liver failure as well as untreatable cancers. Roughly half of the people who contract the disease will eventually clear the virus, but doctors have no effective way to combat the infection in the other half.

The RNA-based therapy “goes to the root of the problem better than any antivirals I’ve seen,” comments Rajan George, senior vice president for research and development at ViRexx, an Edmonton, Canada–based immunotherapy company.

The RNA molecule works by activating a system of seek-and-destroy enzymes in the liver cells. This system uses the genetic code in the RNA as a template for finding and cutting up molecular precursors of the viral replication enzyme, a process called RNA interference.

In previous research, McCaffrey’s team found an RNA segment that could block replication of the hepatitis virus, but mice given the RNA died after about 30 days because the RNA accumulated in the body and became toxic.

To fix the toxicity issue, McCaffrey and his colleagues compared the toxic RNA with other RNA segments that the mice’s liver cells naturally use for the seek-and-destroy system. By tweaking the genetic code in the RNA snippet to make it more like the natural RNAs, the scientists made the snippet more compatible with the liver cells.

Mice given the modified RNA lived for more than 75 days with no signs of toxicity. While the research could eventually lead to a new treatment for chronic hepatitis B infection, more safety research on animals is needed before the therapy will be ready for clinical trials on people, McCaffrey says.

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