New Approach to Treating Pneumonia in Immunosuppressed Populations

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Pneumocystis carinii is a tiny parasite that preys on those with weakened immune systems--premature infants, people with AIDS, people with cancer, and organ transplant recipients. It produces pneumonia in its victims, making them gasp for air and turn eerily blue from lack of oxygen. If not treated, it is almost always fatal.

Fortunately, the disease is currently treatable with an inexpensive antibiotic. But because microbial diseases are becoming increasingly resistant to existing drugs, scientists are always looking for new treatments. A group of basic researchers recently devised an entirely new approach to treating Pneumocystis carinii pneumonia.

Instead of screening a vast range of natural products, which is how most drugs have been discovered, these researchers are specifically targeting the essential core of the parasite--its genetic material. The researchers focused on RNA, a genetic material that is similar to DNA, but is a step closer to protein synthesis. They designed a short "antisense" RNA molecule that binds to a section of RNA in the organism. This particular section of RNA is an excellent target, because it is critical for the parasite's survival and it is not present in humans, so drugs that target it are less likely to produce unwanted side effects in people.

The synthetic RNA molecule is called "antisense" because its genetic sequence is biochemically complementary to--and therefore binds to--its target, the "sense" molecule. Because the synthetic molecule takes advantage of the shape as well as the sequence of its target, it binds 1,000 to 100,000 times more tightly to the target than would be expected based on sequence alone.

When bound to the target RNA strand, the synthetic RNA disrupts the normal process by which P. carinii cells construct protein-making machines called ribosomes. Without being able to properly construct ribosomes, the organism can no longer grow or reproduce and thus loses its ability to cause disease.

Because the synthetic RNA molecules produced by these researchers are small (6 nucleotides long, rather than the typical 15-20 used in similar strategies), they are easier and cheaper to synthesize. The researchers also modified the molecule to resist degradation by enzymes in the human body.

Although the work was done in a laboratory environment, rather than in people, the success of the work proves that the approach is worth pursuing. Researchers may find additional targets in P. carinii, and may also find important RNA targets in other disease-causing microbes.


Testa SM, Gryaznov SM, Turner DH. In vitro suicide inhibition of self-splicing of a group I intron from Pneumocystis carinii by an N 3' --> P 5' phosphoramidate hexanucleotide. Proc Natl Acad Sci USA, 1999;96:2734-9.

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