A new tool that blocks disease-causing genes, RNA interference, could lead the way for the next wave of blockbuster drugs in biotechnology.

But investors and the public have heard that so many times before that even the companies involved in the research are shying away from too much publicity and hype.

Scientists and venture capitalists are comparing RNA interference, or RNAi, to the recombinant DNA revolution that launched the entire biotechnology industry in 1976 when Genentech began its operations.

Fortune has dubbed RNA interference biotech’s next “billion dollar breakthrough” in a cover story. Science named it the “breakthrough of the year” for 2002. But such lofty claims are making people nervous. The handful of companies getting venture capital money for businesses based on RNA want to keep the hype down, having learned from previous overzealousness.

“The first time (RNA interference) doesn’t work, Wall Street will think it’s completely worthless,” said Jonathan MacQuitty, president of Abingworth Management, who mediated an MIT/Stanford Venture Lab panel Tuesday.

Christoph Westphal, founder of Alnylam Pharmaceuticals and general partner at Polaris Venture Partners, also downplayed the hype, saying it would be a decade before anyone knew if the technology would work as a human therapeutic.

Still, Westphal and the handful of private companies writing business plans based on RNA interference are just barely containing their enthusiasm. In the same hour, Nassim Usman, chief scientific officer and vice president of research and development at Sirna Therapeutics, said, “I’m confident there will be a drug made form this technology in the next 10 years.”

He and others say they believe the technology has more promise than similar technologies that didn’t live up to their promise. One that these researchers often mention is antisense. RNAi researchers are quick to distance themselves from antisense, which was a sensation in the biotech world in the 1980s.

Antisense technology is very similar to RNAi — it blocks the function of disease-causing genes. Some key studies didn’t show positive results, and antisense was declared a letdown.

But Isis Pharmaceuticals researchers disagree that antisense was a failure. They introduced the first drug to the market based on the technology, and have several others in late-stage trials.

“I think it’s like any other technology where there are going to be hurdles that you have to overcome,” said Frank Bennett, vice president of antisense research at Isis in a phone interview. “I think it was perhaps over-promised in the beginning but I’m very happy with antisense,” said Bennett, who was also on the panel.

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