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Harvard Scientists Build DNA ‘Cages’

Tiny structures could be used for drug delivery

Scientists at Harvard University's Wyss Institute have built a set of self-assembling DNA cages one-tenth as wide as a bacterium. The structures are some of the largest and most complex structures ever constructed solely from DNA, according to a report in the March 13 online edition of Science.

In the future, scientists could potentially coat the DNA cages to enclose their contents, packaging drugs for delivery to tissues, the researchers say. And, like a roomy closet, the cage could be modified with chemical hooks that could be used to hang other components, such as proteins or gold nanoparticles. This could help scientists build a variety of technologies, including tiny power plants, miniscule factories that produce specialty chemicals, or high-sensitivity photonic sensors that diagnose disease by detecting molecules produced by abnormal tissue.

Scientists in the emerging field of DNA nanotechnology are exploring ways to use it to build tiny structures for a variety of applications. These structures are programmable, in that scientists can specify the sequence of letters, or bases, in the DNA, and those sequences then determine the structure it creates.

So far, most researchers in the field have used a method called DNA origami, in which short strands of DNA staple two or three separate segments of a much longer strand together, causing that strand to fold into a precise shape.

At Harvard, scientist Peng Yin, PhD, and his colleagues first used DNA origami to create extra-large building blocks in the shape of a photographer’s tripod. The plan was to engineer the legs of the tripod to attach end-to-end to form polyhedra — objects with many flat faces that are themselves triangles, rectangles, or other polygons.

But when Yin and his co-workers built bigger tripods and tried to assemble them into polyhedra, the large tripods’ legs would splay and wobble, which kept them from forming polyhedra at all. The researchers got around that problem by building in a horizontal strut to stabilize each pair of legs, just as a furniture maker would use a piece of wood to bridge the legs of a wobbly chair.

To glue the tripod legs together end-to-end, they took advantage of the fact that matching DNA strands pair up and adhere to each other. They left a tag of DNA hanging off a tripod leg, and a matching tag on the leg of a different tripod with which they wanted it to pair.

The team programmed DNA to fold into sturdy tripods 60 times larger than previous DNA tripod-like building blocks. The tripods then self-assembled into a specific type of three-dimensional polyhedron — all in a single test tube.

By adjusting the length of the strut, Yin and his colleagues built tripods that ranged from upright to splay-legged. More-upright tripods formed polyhedra with fewer faces and sharper angles, such as a tetrahedron, which has four triangular faces. More splay-legged tripods formed polyhedra with more faces, such as a hexagonal prism, which is shaped like a wheel of cheese and has eight faces, including its top and bottom.

In all, the scientists created five polyhedra: a tetrahedron, a triangular prism, a cube, a pentagonal prism, and a hexagonal prism.

Source: Harvard University; March 13, 2014.

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