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siRNA Selection Serendipity

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Andy Fire and Craig Mello are having their day in the sun. They’ve been awarded the first US patent in RNA-mediated interference and their names are known worldwide to anyone who’s relying on their discovery to conduct RNAi-based gene function analysis, target validation, or therapeutic development.

Tom Tuschl seems to be in the prime of his career too. The 36-year-old researcher, widely considered the world’s leading expert on short interfering RNAs, moved his laboratory of RNA molecular biology earlier this year to the tony Rockefeller University campus, where his staff works in a sunlit lab with views of the East River and New York skyline — a position he says he accepted in order “to not be second class” in the field. With the time he spends sitting for photographers and explaining his work to reporters (including a generous three hours in his office with this one), it’s hard to imagine how he gets much work done. But his discoveries are revered by many as Nobel prize-caliber.

There’s also Phil Zamore, Dave Bartel, and Greg Hannon — three more rising stars stirring up this revolution in functional genomics with further advances in RNA interference methods. In Europe there’s Roland Kreutzer and Stefan Limmer, who left their University of Bayreuth labs behind five years ago to embark on a commercial pursuit of RNAi therapeutics. And across the world there are now scores of researchers using and perfecting RNA interference, filing papers and patent applications by the day.

With all this fresh biology brilliance around, what, you may ask, prompted us to put old-timer Phil Sharp on the cover of our RNAi issue? Call it a combination of serendipity and our attempt at savoir-faire.

As the cover story was coming together over the past two months, the question of whose face belonged on the cover loomed. Paul, our art director, was losing patience; I couldn’t decide. So many scientists deserve credit for this new technology, and the work of each one has built on the others’.

Then, by the time I was so deeply involved in researching this topic that I was finding RNAi anagrams embedded in my own name, I stumbled upon Sharp’s portrait hanging in a genomics art exhibit in New York. The striking 80”x60” gelatin silver print of the scientist and his string (he told the artist that it represents his 1977 discovery of spliced RNA for which he won the Nobel Prize in 1993) was a GT cover waiting to happen. Sharp, who founded Biogen in 1978 and directs MIT’s new McGovern Institute for Brain Research, seemed the perfect solution. Not only is he the senior-most person named on any of the new RNAi IP, but he has also mentored several of the next-generation scientists working in the area. Just last year Sharp founded Alnylam, a company that aims to develop siRNA therapeutics, with his collaborators Bartel, Tuschl, and Zamore.

MIT says Sharp’s earlier prize-winning work “opened an entirely new area in molecular biology and forever changed the field.” With their new methods for silencing genes, he and his progeny are doing it again.

This month’s RNAi coverage is the first of a series. Here we present an overview of the RNAi revolution — a look at the market for siRNAs, pharma’s incorporation of RNAi into target validation programs, and the academic world’s pursuit of whole-genome RNAi screening projects. In the coming months, we’ll follow up with more in-depth reporting on each of these areas as the field unfolds.

Adrienne J. Burke, Editor in Chief

Also coming next month in GT:

• Mass spectrometry goes hybrid

• We rank the Genome Technology Index CEOs

• IT Guy takes a hike on the pathway databases

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