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Interference From RNA Stymies Hepatitis B
12 May 2003 (All day)
Millions of RNA molecules can protect mice from the damage wrought by hepatitis B, a new study shows. The technique disables the virus's genes. The find takes scientists a step closer to using this novel approach, called RNA interference (RNAi), in people.
Researchers discovered in the late 1990s that shortened RNA molecules could turn off specific genes. In recent years, some biologists have begun studying how these so-called small interfering RNAs (siRNAs) can be used to squelch disease. In February, a team reported using siRNAs to shut down a gene in the liver in mice and protect it from an inflammatory attack resembling hepatitis (ScienceNOW, 10 February. Gene therapist Mark Kay and his postdoctoral student Anton McCaffrey, both of Stanford University in California, and their colleagues wanted to know whether RNAi could target the virus behind hepatitis directly--the only way to ultimately cure people of the disease.
The researchers first mimicked a hepatitis B infection by inserting the hepatitis B genome into liver cells in mice. Then they turned to two kinds of siRNAs, each of which targets different portions of the hepatitis genome. Kay's team placed the siRNAs into loops of DNA called plasmids. Infusing the mice with massive numbers of these plasmids under high pressure left the animals with up to 92% less hepatitis B RNA than control animals, the researchers report in the 12 May issue of Nature Biotechnology. The mice suffered no detectable serious side effects, although Kay points out that this delivery method cannot be used in humans. He and others are experimenting with more benign ways to reach large numbers of cells with siRNAs.
Judy Lieberman of Harvard University, a lead author on the February hepatitis paper that used a different approach, is heartened that Kay's study was successful but cautions that many hurdles remain. Philip Sharp of the Massachusetts Institute of Technology in Cambridge agrees. "The issue is, can you get [siRNAs] there efficiently, adequately, to impact on the process that's causing disease?" he says. "I remain optimistic, but I don't consider it a dead certainty."