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See Inside January 2008

Getting from Here to There

A protein borrowed from the rabies virus gets a drug to where it is needed

As hard as it is for scientists to develop new drugs, sometimes just getting the drug to where it needs to act is equally challenging. Nowhere is this more true than in the brain, where blood vessel walls are tightly knit, keeping most large molecules from seeping out of the bloodstream and into brain tissue. This blood-brain barrier is a formidable obstacle to delivering certain types of treatments for neurological diseases, but Manjunath N. Swamy and his team at Harvard Medical School's Immune Disease Institute devised a clever way to sneak a drug through and insert it directly into brain cells.

Some viruses that specialize in infecting the nervous system, such as rabies and herpes, are adept at penetrating the blood-brain barrier. Swamy's group exploited that capability by disguising a drug with a small protein normally found on the surface of the rabies virus. The protein is believed to unlock a passageway through the blood vessel walls, and a drug molecule hitched to the viral protein was able to penetrate the barrier. Once inside the brain, the protein also allowed the drug to enter individual nerve cells, much as a virus would infect them. The therapeutic molecule used in Swamy's experiments was a small nucleic acid chain, known as a short-interfering RNA (siRNA), which can be customized to target specific genes and suppress their effects, making siRNA delivered straight to the brain a versatile tool for a wide range of uses.

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