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It’s champagne for everybody. Phil Zamore pops the cork from a bottle of Montaudon, drenching the brand-new carpet. Everyone in his lab fills a glass to toast the boss. “Unexpected good news,” he explains. Zamore, a biochemist at the University of Massachusetts Medical School in Worcester, has just received a national award worth $1 million over five years. “The budget of the lab just tripled.”

Zamore is understandably giddy, and it’s not just about the money. Zamore’s field, RNA interference, or RNAi, is only a few years old, but it has taken the world of biology by storm. “RNAi is the most exciting insight in biology in the past decade or two,” says Nobel laureate Phillip Sharp, a biologist at MIT. And Zamore’s lab is one of a handful moving the field forward at a dizzying pace. “I think everybody who works in the field feels a bit breathless from the progress,” Zamore says.

The sense of excitement shared by Zamore, Sharp, and other researchers is well-founded. For decades, researchers thought RNA was merely DNA’s messenger, slavishly delivering DNA’s protein blueprints. But it now appears that tiny double strands of RNA, introduced into lab-grown cells or animals, can quickly and efficiently turn off any given gene.

The implications are breathtaking, because living organisms are largely defined by the exquisitely orchestrated switching on and off of genes. Biologists, until now, have only been able to mimic this switching process in a slow, ponderous, and indirect way. But the ease with which RNAi can turn off genes, researchers say, seems almost mystical. Laboratory techniques using RNAi are already biologists’ methods of choice for discovering the functions of particular genes. And it promises a new way to treat disease directly by shutting down key genes involved in various ailments. Already, at least eight companies-including one founded by Zamore, Sharp, and colleagues-are working on RNAi therapies for everything from viral diseases to cancer.

“The Holy Grail is to develop all this into drugs,” says Zamore. “To be able to give you a small interfering RNA that would shut off expression of your high-cholesterol gene. That would lower the level of hepatitis C infecting your liver. Or maybe, I think in perhaps the biggest pie-in-the-sky application, that would hone in on a gene specific to tumor cells and kill the tumor.”

How soon this might happen is anybody’s guess. RNA interference burst into the consciousness of the scientific world at the annual meeting of the RNA Society in Banff, Alberta, in May 2001. There, Sayda Elbashir, a postdoc in the lab of biochemist Thomas Tuschl at the Max Planck Institute for Biophysical Chemistry in Gttingen, Germany, stunned his listeners with the news that tiny double-stranded RNA fragments quickly, easily, and specifically turned off genes in human cells, a role researchers had never before seen RNA play.

“Most of the audience was just sitting there saying to themselves, Science has just changed,’” recalls University of Michigan biochemist David Engelke. “The only thing that prevented pandemonium was that we’d been promised this sort of thing before.” Skeptical, Engelke waited a few months. “Then these reports started to trickle in: Gee, this really works!’”


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