The technique could help patients with currently untreatable diseases such as Huntington's.

RNA Rx: An Alynlam chemist prepares RNA molecules. Alnylam Pharmaceuticals

A biotech company called Alnylam announced today that a small clinical trial for a genetic therapy based on RNA interference, or RNAi, suggests that the technique can have a powerful effect on its target gene. The therapeutic effect lasted for over a month with just one dose. The company is also working with a medical device maker, Medtronic, on a way to deliver RNAi treatment directly to the brain, in order to treat the degenerative brain disease Huntington's.

The patients in the trial have a genetic disorder that originates in the liver and leads to the buildup of protein deposits in many organs. Alnylam, a Cambridge, Massachusetts-based company, says its RNAi therapeutic, given at its highest dose, reduces the amount of the faulty protein that spurs the disease by almost 94 percent.

The positive results add weight to the notion that RNAi therapeutics could eventually help patients with a range of genetic diseases. RNAi therapy involves researchers producing snippets of RNA, a close relative of DNA, that match a portion of a gene of interest. When administered, this so-called small interfering RNA (siRNA) causes the destruction of that gene's products before it can be turned into a protein. The specificity of RNAi for targeting particular genes has attracted a lot of interest from people who want to use it as a clinical treatment (see "Prescription RNA").

"Today's platforms target the protein that causes the disease and bind to that protein. We stop the protein from being made in the first place," says Barry Greene, president and chief operating officer of Alnylam.

But a recurring challenge for the therapeutic RNAi field is how to deliver the siRNAs to the right place in the body. On their own, the small molecules do not survive long in the bloodstream, so simply injecting a patient with a solution of unprotected siRNAs is not effective. "The key technical hurdle is getting the siRNA [inside] the right cells," says Greene.

For several of its projects, Alnylam uses nanoparticles to protect and deliver its siRNAs, which can then be delivered by injection. But for genetic diseases that originate in the brain, the body's own defenses, namely the blood-brain barrier, complicate delivery further. To circumvent the blood-brain barrier, which prevents most molecules from leaving the bloodstream and entering the brain, Alnylam has looked to a different delivery mechanism: direct dosing of unpackaged siRNAs.

Medtronic, a Minneapolis company that designs and manufactures medical devices, has devised a way to allow this. Together, the companies have developed a treatment that combines Alnylam's RNAi therapeutic with Medtronic's drug delivery technology to treat Huntington's.

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Gene Control, Delivered Directly to the Brain

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