armored. The mouse livers that received siRNA targeting Fas gene were protected against hepatitis (right), unlike those given saline placebo (left).
Shooting millions of tiny RNA molecules in the blood of mice can protect the liver against the ravages of hepatitis. This is apparently the first time that this technique, called RNA interference (RNAi) was used to fight against the disease in an animal. But biologists warn that the therapy has a long way to go before it can be safely applied to humans.
RNAi uses thumbnails RNA molecules to silence specific genes ( Science NOW, December 19, 02). Normally, large RNA molecules convert genetic information into protein; but in the late 190s, researchers found that the truncated RNA could be induced to turn off genes. Hepatitis has become a center RNAi studies, because the liver easily absorbs molecules.
Harvard University immunologist Judy Lieberman and Premlata Shankar and colleagues wanted to see whether RNAi could prevent liver damage. They gave mice three injections massive high pressure - equivalent to about half the volume of blood "animals - a solution that forced the molecules in the liver. The molecules are designed to stop a gene called Fas , which when overactive, induces liver cells to self-destruction; Fas is also involved in human liver diseases.
The next day, the animals received an antibody that sends Fas in hyperdrive, causing liver failure. Control mice died within a few days, but 82% of the treated mice survived. About 80% to 0% of liver cells incorporated RNA molecules. In addition, RNA molecules hung around for 3 weeks, about three times longer than previous studies, the authors report online today in Nature Medicine
During this time, other mice face a distinct challenge :. Over six weeks, they received weekly injections of cells called Con, which Goad the immune system to attack the liver, producing the kind of scars seen in viral hepatitis. Some animals also received an RNA infusion during this time, and this group developed any damage to the liver. Despite the traumatic delivery method, the mouse does not seem to suffer any side effects.
"It is amazing how it worked," marvels Charles Rice of the Rockefeller University in New York City Still, he added, the delivery method is clearly problematic. In humans, the "hydrodynamic shock ... is not the way to go." Researchers have yet to determine if a more gentle approach might prove fruitful.
Related Sites
The homepage of Judy Lieberman
General Hepatitis Foundation International
Hepatitis C Information from NIH
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