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News and Views

Vol 459|21 May 2009NANOTECHNOLOGYAnother dimension for DNA artThomas H. LaBeanNEWS & VIEWSMany of nature’s intricate nanostructures self-assemble from subunits. Efforts to mimic these assemblyprocesses enter a new phase with a method to design and build three-dimensional DNA nanostructures.Through the ages, some of the most iconic andlasting artefacts of human ingenuity have beensculptures and carvings, created from a widevariety of materials. But until now, a generalpurposematerial from which nanometre-scale,three-dimensional shapes could be made hasbeen lacking. On page 414 of this issue, Douglaset al. 1 introduce a clever method for fabricatingnanometre-scale objects from DNA, andreport the construction of several such objects.The authors describe their method as “analogousto sculpture from a porous crystallineblock”, except that the structure of their blockconsists of tubes — DNA double helices —arranged in a regular honeycomb lattice. Thedesired shapes are not literally carved into thestarting material, but instead form from DNAthat has been designed to self-assemble into asupramolecular complex.The use of DNA as a construction material formaking nanometre-scale objects began morethan 25 years ago 2 , and has since developed intothe field of structural DNA nano technology 3,4 .The field relies on the fact that molecularrecognition and assembly of DNA can beprogrammed so that it forms designed nanostructures.Such programming is enabled by ourunderstanding of Watson–Crick base pairing:for any DNA base sequence, we can immediatelydetermine the complementary sequence,and know that the two molecules will find andbind to one another in water under appropriateconditions. Well-developed synthesis techniquesallow DNA strands of any desired basesequence to be easily prepared.In 1998, DNA nanotechnology was transformedby the introduction of the ‘tile andlattice’ strategy 5 . Tiles are nanometre-scalebuilding blocks that fold independently, andtypically contain domains of DNA doublehelices tethered by ‘strand-exchange points’.These points model naturally occurring junctionsthat form in genetic-recombination complexeswhen DNA strands are traded betweenhelices. Short, single-stranded DNA segmentshang off the tiles at strategic locations. On coolingin solution, the single-stranded segmentson different tiles bind to each other, so thatthe tiles assemble into larger, predominantlytwo-dimensional lattices.aFigure 1 | DNA sculpture. Douglas et al. 1 report a method for designing and constructing threedimensionalnanostructures from DNA. a, The computer-aided design process begins with a blockof tubes arranged in a honeycomb lattice. b, A template for the desired DNA structure is designed byremoving sections of the tubes, just like carving a sculpture from a block. The remaining tubes willbecome DNA duplexes in the final object. The DNA structure is designed by routing a single-strandedscaffold DNA (a virus genome) through every section of the tube template. Hundreds of short strandsof DNA are then designed to bind to the folded scaffold, cross-linking between different tubes and‘stapling’ together the overall structure. When the staple molecules are synthesized and mixed with thescaffold DNA in solution under appropriate conditions, they direct the folding of the scaffold into thedesired nanostructure. The structure shown here is more complex than those prepared by the authors(see Fig. 2 on page 416).bAnother conceptual leap occurred in 2006,with the demonstration of DNA ‘origami’ 6 .This strategy uses a long, single-strandedDNA — for example, the genome of the M13virus — as a scaffold molecule that is foldedback and forth on itself to form a planar raftof double helices. The resulting structure isknitted together by a few hundred short, syntheticDNA molecules that act as staples, linkingtogether the helices at appropriately spacedstrand-exchange points. The raster-like routingof DNA scaffolds through origami structuresprovides a general system for makingnanometre-scale, two-dimensional sheetsof any shape, and with any desired surfacepattern. But given the flat raft architecture,© 2009 Macmillan Publishers Limited. All rights reserved331

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