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Biomedicine

DNA Building Blocks

New pyramidal structures made out of DNA could be the basis of complex molecular devices.

For years, some researchers have suggested that DNA could be used to create complex self-assembling structures and even nanoscale machines. Indeed, simple shapes, such as cubes, and simple devices, such as tweezers, made of DNA have already been created. But skeptics have questioned whether DNA has the stability needed for more sophisticated devices.

Now researchers from The University of Oxford have developed rigid building blocks out of DNA that can be designed to self-assemble into more complex structures. These blocks, which are shaped like pyramids, have already demonstrated their usefulness by enabling the first measurements of the amount of force that DNA can support without buckling, according to the researchers.

Andrew Turberfield, professor of physics at Oxford, and a researcher involved in the work, says it is “one of the very few examples of the use of a DNA nanostructure to allow you to actually do something that you couldn’t do before. It doesn’t just look pretty, it’s actually useful.”

The new measurements show that DNA is “a relatively strong material,” says Chris Dwyer, electrical and computer engineering professor at Duke University, who also works on DNA self-assembly. “This solidifies the argument that we’ll be able to use DNA self-assembly for more complex structures.”

DNA is an attractive material for self-assembled devices because its sequence of bases, which in the body serve as the genetic code, can be “programmed.” By tweaking this code, researchers are able to direct how strands will combine when added to a solution.

In the work at Oxford, four strands of DNA served as the basis for the pyramids. Each strand makes up one triangular face. The edges of these triangles have open puzzle-piece sequences that bind to another edge of a triangle. As these edges meet, the triangles fold into the shape of a pyramid. Simply by mixing the right numbers of different strands together, the researchers have built trillions of pyramids – and in just seconds.

These simple structures may prove to be useful as containers, perhaps for drug delivery in the body. But they are also rigid structures that could be a starting point for many other, more complex structures. To get these building blocks to assemble into more complex structures, the Oxford researchers again turned to DNA. They incorporated loose strands into the structures with sequences designed to link to loose strands in neighboring pyramids.

So far, they’ve used this technique only to form pairs of pyramids. But they say it should be possible to hook many more together. By varying the sequences used and where they’re placed in the pyramids, such as at the edges or the points, the researchers say their pyramids could self-assemble into a variety of shapes. They hope DNA can readily serve as a scaffold for arranging other materials.

“It’s a great way of laying out an architecture with essentially atomic precision,” says Turberfield, “but to make some sort of useful molecular device, you’re almost certainly going to want to link other things, for example, molecular electronic components, to scaffolding like this to make a complete device.” Such components could include nanowires, which could lead to three-dimensional circuitry, perhaps for dense and powerful computers. They might also incorporate biological molecules for sensing or fluorescing chemicals for imaging applications.

The biggest advantage of these pyramids may actually be their initial lack of complexity. Patrick Doyle, an MIT chemical engineering professor who studies the dynamics of DNA, says the design is “rather elegant.”

In the past, three-dimensional DNA structures were built with a painstaking series of steps, and ultimately produced few copies. These pyramids, however, which are formed with the aid of heating, then cooling the DNA strands, take only one step to assemble and produce much higher yields.

“One of the virtues of this structure is the extreme simplicity and very high yield and speed of synthesis,” says Turberfield. “If you want a building block to make lots of other things with, you don’t want to be toiling over the construction of the building block – you want that to be easy. Then you can go on to do the harder stuff, by linking it later.”

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