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Magdalena Koziol, a former postdoc at Yale University, was the victim of scientific sabotage. Now, she is suing the...
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RNA Therapy Curbs Lung Damage
6 November 1997 8:00 pm
By injecting short nucleic acids into rats, researchers have blocked an enzyme linked to swelling and tissue damage in the lungs. The researchers hope to turn this novel compound, described in the latest issue of Current Biology, into a drug to prevent heart failure due to acute respiratory distress syndrome, which kills about 75,000 people each year in the United States.
In respiratory distress syndrome, and possibly other lung diseases, the immune system overreacts to trauma or infection. White blood cells called neutrophils flock to the lungs, releasing tissue-damaging enzymes such as elastase. To try to block elastase, biochemist Drew Smith of NeXstar Pharmaceuticals in Boulder, Colorado, earlier this year synthesized a nucleic acid sequence called an aptamer, which is designed for its shape. This aptamer, called NX21909, was designed to fit into the active site of elastase. As a result, it strongly bound elastase in the test tube, preventing the enzyme from degrading connective tissue.
To test the aptamer's mettle in animals, Smith and his colleagues provoked a strong immune response in rat lungs. They did this by injecting antibodies to a cow protein into rat lungs, then added the protein itself, which led to swelling and tissue damage. Nine rats were given this treatment alone, while 22 received varying doses of NX21909. The higher the dose, the less likely that blood would leak into the lungs, a sign of damage caused by elastase. In rats given the highest dose, lung leakage was 38% less than in controls.
The work "is one of the first studies showing that aptamers can be used as drugs," says Michael Famulok, an aptamer researcher at the Max Planck Institut für Biochemie in Munich, Germany. And because aptamers are easily synthesized by machine, Smith says they may be cheaper and easier to make than drugs produced by cell culture. Treating a human disease with aptamers is still "a leap, but in principle we can do this," says Smith.