In 1996 Worth magazine proclaimed that Isis Pharmaceuticals could become the next Microsoft, a prediction that turned out to be a particularly egregious example of hyperbole run amok. To be sure, Isis remains a leader in the gene-blocking technology called antisense. But the road to successful treatments for cancer and other diseases has been littered with disappointments. During the past few years, a new gene-silencing technology has emerged that may be poised to fulfill the promise that was once trumpeted for antisense. “I’ve been writing in grants for 25 years that during the next five years I’m going to test this process or that process to see if I can do gene inactivation studies in mammalian cells in culture. And I did them, and they were so awkward and so complicated that you just couldn’t apply them generally,” says Phillip A. Sharp, director of the McGovern Institute for Brain Research at the Massachusetts Institute of Technology.