Roche Unveils Tamiflu Production Network - C&EN Global Enterprise

Mar 20, 2006 - ... the active ingredient in Tamiflu, an antiviral being stockpiled by governments around the world as a defense against the H5N1 avian...
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in DNA nanotechnology and has built an origami system that allows the formation of arbitrary patterns with what appears to be relatively little effort and expense," says New York University chemistry professor and DNA nanotechnology pioneer NadNANOART rian C. Seeman. T A SCALE OF 1:200 TRILLION, it for years to build These colorized "This is an exPaulW.K.Rothemund's nanoscale cubes, atomic force citing advance, new map of the Americas cages, and octamicrographs, each which is likely to won't help anyone trying to navi- hedrons. Now, just a few hundred revolutionize patgate a cross-country road trip. But with his so-called * tern formation on nanometers across, the simple, universal design scheme DNA origami, this scale." show the versatility that the California Institute of R o t h e m u n d Rothemund starts of DNA origami. Technology computer scientist has taken DNA the origami process by invented to create the image—just nanofabrication to a new sketching out the nanoa few hundred nanometers across level, creating DNA nanodesigns and made entirely of DNA—of- 10-fold more complex than any structure's desired shape on his computer. To this sketch, he comfers scientists a stunningly simple made previously. and versatile route to create nanoWith DNA origami, putationallyfitsthe structure's long, structuresfromthe bottom Rothemund can knit single-stranded DNA scaffold and up {Nature 2006, the nucleic acid into hundreds of short pieces of DNA 440,297). any two-dimension- that will staple the scaffold rigidly al shape or pattern. in place. Design in hand, RotheDNAs regStars, snowflakes, mund mixes the component nucleic ular structure and smiley faces acids together and anneals them for and predictable just 100 nm wide a couple of hours to generate the chemistry make are among his final structure in good to excellent it an ideal building yields. He says each nanostructure tiny creations. block for bottom"Rothemund takes about two weeks to realize up fabrication. Scien has taken a new step from concept to construction. tists have been using "Rothemund's work not only presents stunningly successful PANDEMIC PREPAREDNESS engineered molecular assemblies, but it simultaneously disproves three long-held tenets of DNA nanoconstruction," notes Thomas oche has signed agreements with more than 15 external contractors to help it expand production of oseltamivir, the active ingredient in Tamiflu, an antiviral being stockpiled by governments H. LaBean, a professor of chemisaround the world as a defense against the H5N1 avian flu virus. With the use of intermediates and try and computer science at Duke finished materials from these contractors, Roche says it will be able to produce 400 million flu treatUniversity. "This study has shown ments annually by the end of 2006, up from 300 million currently. that nucleotide sequence at crossThe 13 firms so far revealed to be on the contractor list are a who's who of the global fine chemicals over points need not be carefully industry: Albemarle, Ampac Fine Chemicals, API Corp., Clariant, DSM, FIS, Martek Biosciences, No- optimized and that thorough purification and precise stoichiometric vasep/Dynamit Nobel, PHT International, PPG Industries, Sanofi-Aventis, Shaanxi Jiahe Phytochem, control of synthetic oligonucleand Siegfried. Martek and Sanofi both say they will produce Tamiflus starting material, shikimic acid, via fermenta- otides are unnecessary." Scientists see potential for DNA tion—Martek in Kingstree, S.C., and Sanofi in Saint-Aubin-les-Elbeuf, France. Roche has been obtaining origami in areas as diverse as elecshikimic acid largely via extraction from Chinese star anise fruit, but supplies from this source are limited. Clariant will produce a shikimic acid derivative known as epoxide at a U.S. plant, and Novasep will tronics and molecular biology. "In produce a downstream azide intermediate in Germany. addition to the obvious potential Roche earlier signed sublicenses for complete oseltamivir production with India's Hetero and China's impact on assembly of functional nanoscale materials and molecular Shanghai Pharmaceuticals. It now says it is negotiating a production sublicense with another Chinese company and that it is evaluating sharing expertise to enable production in Africa. circuits, since this work utilizes the In addition, Roche says it has launched research initiatives to answer questions about the use of folding of genomic viral DNA, it Tamiflu against the evolving H5N1 virus. According to Roche Pharma CEO William M. Burns, the com- hints at possible future applications pany is "committed to further expanding the knowledge base regarding Tamiflu and the H5N1 virus, in medical diagnostics and therabut we cannot do this alone, and we need to collaborate with third parties moving forward. "—MICHAEL peutics," LaBean adds.—BETHANY

DNA ORIGAMI

Universal design scheme can wind DNA into any two-dimensional shape

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Roche Unveils Tamiflu Production Network

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C & E N / MARCH 2 0 , 2006

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