RNAi

Finding a mouse that, with the aid of drugs, can live with a chronic hepatitis B infection isn’t all that unusual. But the mice being studied last fall at the laboratories of Boulder, Colorado-based Sirna Therapeutics were pretty special.
The viral genes inside the liver cells of these mice were still cranking out their deathly code of destruction. But the message wasn’t getting through and the viral load in the mice’s blood dramatically declined. That’s because Sirna scientists dosed them with a promising new treatment that attacks the messenger RNA, or mRNA, sent out by diseased genes, as opposed to just killing the diseased cells (as chemotherapy does) or attacking the genes themselves (a method plagued by dangerous side effects).
Sirna’s promising treatment is based on the science of RNAi (the i is for interference), which has tremendous promise for treating just about every disease. The positives of the new treatment were first listed publicly in the July issue of Nature Biotechnology. Very low doses were effective, and the treatment showed no toxic side effects. The drug easily crossed the membranes of the targeted cells, thanks to its encapsulation inside molecules of fatty acids.
And the drug worked rather well. It reduced the viral load in the blood of the infected mice by up to 95 percent.
“The effect was very dramatic,” said Yosef Shaul, a molecular genetics professor at the Weizmann Institute of Science in Rehovot, Israel. Shaul’s team was the first to prove that RNAi-based drugs might work as a weapon against hepatitis. “This is no cure for the disease, but it does show an excellent way to deliver an RNAi drug to the right cell. That’s an important breakthrough.”
Despite the exciting results, Sirna is not developing this particular drug candidate any further because good conventional treatments, including drugs and vaccines, already exist for hepatitis B. Instead, the company hopes to translate its results into a treatment for B’s deadlier cousin, the hepatitis C virus, or HCV. The company says it will begin human trials in 2006.
Hepatitis, though, is just the first step. The market for RNAi-based drugs as a whole could be enormous. There is no disease that affects humans that doesn’t have a genetic component, and RNAi sequences can be tailored to block just about any gene. They do so by binding and then degrading the mRNA produced by the gene before that mRNA can start producing a harmful protein, which actually causes the illness.
Wired has more…
Read more at Sirna Therapeutics…
And some more at the National Science Foundation…