Scientists target microbe with sleeker antisense agent

Scientists at the University of Rochester have created a remarkably short "antisense" compound, just a few nucleotides long, that targets the strain of pneumonia which kills many AIDS patients and others with weakened immune systems. While the compound is in its earliest stages of development, scientists believe the work marks one step toward an era when tiny artificial RNA molecules act as selective medications that knock out vital sections of molecules which organisms rely on to invade their human hosts.

Led by Douglas H. Turner, a team of researchers at the University tested its technology, where scientists create a complementary copy of a strand of RNA in an attempt to knock out a specific RNA molecule from the organism Pneumocystis carinii. This fungus is an opportunistic pathogen that lives dormant in the lungs of healthy individuals, but flourishes in people with impaired immune systems, causing pneumonia and leaving its victims gasping for breath. More than half of AIDS patients are infected by the microbe at some point in their lives, and more than 20 percent ultimately die from an infection; cancer patients and people who have received organ transplants are also susceptible.

The Rochester team blocked the formation of a strand of RNA that the organism needs to survive. While the work was done in a test tube, it's a first step toward designing drugs to treat this class of infections. The need for new anti-fungal medications is clear, says Turner: "The problem is that the bugs evolve. They're getting resistant to the standard treatments."

The National Institutes of Health (NIH) funded the study conducted by Turner, a professor of chemistry; Stephen M. Testa, formerly a post doctoral research associate now at the University of Kentucky; and Sergei M. Gryaznov, a chemist from Geron Corp., a California bio-tech company that supplied molecules for the project. The results were published recently in the Proceedings of the National Academy of Scien

Contact: Susan Murphy
University of Rochester

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