331-338 News & Views MH.indd

three-dimensional objects. Douglas and colleagues’ work represents a third revolution in DNA nanotechnology. They have extended the DNA origami technique by showing how a DNA scaffold strand can form layers of helices arranged in a honeycomb lattice, thus providing a general-purpose, crystalline material from which three-dimensional objects can be constructed. In principle, any shape can be made from this DNA material, as long as it can be ‘carved out’ from a block of the honeycomb lattice. To design their nanostructures, the authors devised a computer-aided process that begins with a template block composed of tubes (Fig. 1); each tube becomes a DNA duplex in the final structure. Once a target shape has been defined by removing sections of the block, a single-stranded scaffold DNA (the M13 virus genome, as in flat DNA origami) is routed through every part of the structure, and complementary ‘staple’ strands are designed to bind to the scaffold and thus create duplexes. Finally, strand-exchange points are defined between neighbouring double helices. Enough of these junctions must be used to stabilize the overall structure, while still maintaining enough flexibility in the system to allow the desired shape to assemble. Having drawn up plans for their target structures, Douglas et al. heated, then very slowly cooled, a solution of the scaffold DNA and its hundreds of staples. Under these conditions, the staples directed the folding of the scaffolds into the desired shapes. Douglas and colleagues’ approach can be compared with a recently published procedure for three-dimensional DNA origami, in which a hollow box (42 × 36 × 36 nanometres) was assembled. Two-dimensional DNA origami was used to construct all six flat walls of the box on a single scaffold strand, and then interwall staple strands directed the assembly of the final three-dimensional form. The box design is highly innovative — it even includes a lid that can be opened and closed — but the box gains its three-dimensionality by orienting intrinsically two-dimensional subunits against one another in space. By contrast, the honeycomb lattice technique is inherently three-dimensional from the start of the design process. Of course, the primary goal of DNA nano technology is not to create aesthetically pleasing sculptures, but to make functional devices and materials. For practical applications, structures generated using Douglas and colleagues’ method will probably need to be integrated with other nanomaterials that have electronic, photonic or catalytic properties superior to those of DNA. There are currently also other limitations to the technique. For example, the self-assembly process results in low product yield (providing only about 7–44% of the theoretical yield), proceeds very slowly (taking about a week), and generates products that have an unfavourably high charge density (because the charged DNA backbone is packed tightly in space). Furthermore, the upper limits on the total size of the products and the lower limits on their feature resolution have yet to be determined. The shapes that have been made so far are also somewhat blocky (see Fig. 2 on page 416); the sculpture depicted in Fig. 1b of this article would require either a larger scaffold strand than is currently used, or several such strands. Nevertheless, the potential of Douglas and colleagues’ technique is clear. Hierarchical structures, constructed from several repeating subunits, are a much-sought-after goal of nanotechnology, and the authors present three examples in their paper, including a stunning icosahedron assembled from three M13 genome scaffolds (see Fig. 4 on page 418). This successful move into three dimensions heralds a new era for the field of structural DNA nano technology. ■