RNA INTERFERENCE - C&EN Global Enterprise (ACS Publications)

Oct 9, 2006 - Biologists Andrew Z. Fire of Stanford University School of Medicine and Craig C. Mello of the University of Massachusetts Medical School...
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NEWS OF THE WEEK found that the R N A silenced the genes containing those specific codes {Nature 1998, 391, 806). Since the original discovery, scientists have shown that during R N A i the double-stranded R N A guides the target m R N A to a protein complex known as the RNAinduced silencing complex, which cleaves and thereby inactivates the from specific genes. Biologists AnmRNA. drew Z. Fire of Stanford University School of Medicine and Craig R N A i , w h i c h has also b e e n C.Mello of the Unis h o w n t o w o r k in versity of Massachumammalian cells, is setts Medical School, now a broadly used reWorcester, will split search tool for studythe prize, worth more ng gene function. It than $1.3 million. s also under intense investigation as a poR N A interference, tential therapeutic or RNAi, which preapproach for silencvents genes from being genes responsible ing translated into proteins, is "one of for illnesses. the most significant For researchers in d i s c o v e r i e s in t h e the R N A i field, the p a s t 50 y e a r s . It's only surprise about opened up so many Fire last week's announceavenues for research, ment is how quickly it for therapeutics, for came after the initial thinking about evodiscovery. " R N A i is lution," says John J. a very y o u n g field. Rossi, a molecular Things have gone inbiologist at Beckman redibly quickly," says Research I n s t i t u t e Phillip D. Zamore, an of the City of H o p e RNAi expert and one in Duarte, Calif. "It of Mello's colleagues may not have been as at the University of profound as the disMassachusetts Medicovery of the struccal School. "If you ture of D N A , but it's [had asked] anybody implications are as w h o was going to far-reaching." Mello win the Nobel Prize for RNAi, everyone Fire and Mello unwould say Fire and Mello. It's so earthed RNAi while studying the obvious that their 1998 Nature paregulation ofgene expression in the worm Caenorhabditis elegans. When per changed our whole perception from something weird in worms to the m R N A for making a muscle real biology." protein and the complementary noncoding strand of R N A , the "Over the past few years, it's so-called antisense R N A , were become clear that this {prize} was injected together, the worms belikely to happen one day in the nothaved as if they didn't have the too-distant future," saysJeremy M. functioning muscle protein. Berg, director of N I H ' s National Institute of General Medical SciThe complementary R N A ences, which supports research by strands had combined to form both Fire and Mello. "The impact double-stranded R N A . W h e n of R N A i has been so dramatic alFire a n d M e l l o injected variready, and it's only getting stronous double-stranded R N A molger."—CELIA ARNAUD ecules i n t o t h e i r w o r m s , t h e y

MEDICAL NOBEL PRIZE

RNA INTERFERENCE Two Americans share prize for discovery of RNA gene-silencing mechanism

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HE 2 0 0 6 NOBEL PRIZE IN

Physiology or M e d i c i n e honors the discoverers of R N A interference, the gene-silencing mechanism in which double-stranded R N A instigates the degradation of messenger R N A

P H A R M A C E U T I C A L S

Gilead To Acquire Myogen For $2.5 Billion

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ilead Sciences has agreed to acquire the Denverbased biotechnology firm Myogen for about $2.5 billion. The purchase, expected to close by the end of the year, will expand Gilead's portfolio with ambrisentan (shown), a small-molecule drug for pulmonary arterial hypertension (PAH) that has completed two Phase III clinical trials. The purchase is Gilead's second in recent months aimed at expanding its portfolio beyond its two core HIV treatments. In August, the company completed the $365 million acquisition of Corus Pharma, a developer of drugs for respiratory and infectious diseases. Gilead will pay $52.50 per share for Myogen's stock, a steep 50% premium over its closing price on the day before the deal was announced. In a conference call with stock analysts, Gilead Chief Financial Officer John F. Milligan justified the high price by pointing to other bidders for the company and "the scarcity value associated with products in late stage." Myogen expects to file a New Drug Application for ambrisentan by the end of the year. According to Myogen, PAH is characterized by constriction of the blood vessels in the lungs, a condition that leads to high pulmonary arterial pressures. Ambrisentan, an endothelin receptor antagonist, blocks the negative effects of endothelin, a small peptide hormone associated with blood vessel narrowing. Gilead executives say ambrisentan has a better safety profile than Tracleer, the one endothelin receptor antagonist now on the market. Tracleer, marketed by the Swiss firm Actelion, had $339 million in first-half 2006 sales, up 48% over the first half of 2005. Analysts at Friedman, Billings, Ramsey & Co. predict that ambrisentan could hit annual sales of $600 million.—MICHAEL MCCOY

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