'Antisense' compound targets disease

Turner

S cientists at the University have created a remarkably short "antisense" compound--just a few nucleotides long--that targets the strain of pneumonia that 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. These medications knock out vital sections of molecules that organisms rely on to invade their human hosts.

Led by chemistry Professor Douglas 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 also are susceptible.

The need for new anti-fungal medications is clear, said Turner: "The problem is that the bugs evolve. They're getting resistant to the standard treatments."

In the study, funded by the National Institutes of Health, 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.

"This is exciting because if you figure out a general way to target RNA, then, in theory, you can target almost any disease," said Turner. "Our approach is a new way of designing drugs, built on 15 years of basic research. Even as drugs that use an antisense scheme begin to go on the market, we're trying to create newer, more sophisticated compounds."

The results of the University study were published recently in Proceedings of the National Academy of Sciences.