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Using nothing but DNA, researchers in Denmark have constructed a tiny box with a lid that can either lock shut or–with the help of a set of DNA keys–hinge open. While other groups have experimented with using DNA origami to build three-dimensional objects, the new box, described in this week’s edition of Nature, is distinguished by its solid sides and moving parts.

“It’s a rather beautiful molecular structure,” says John Reif, a distinguished professor of computer science at Duke University, who was not involved in the research. “It’s the first time that a nanostructure like that had a programmable and controllable lid.”

For now, the box serves as a proof of principle that DNA origami can be adapted to make elaborate three-dimensional structures, says Jørgen Kjems, a molecular biologist at the Aarhus University Center for DNA Nanotechnology, who led the research. But in the future, he believes that the nano-sized container could be adapted for a wide range of applications, from drug-delivery vehicle to logic gate.

DNA makes an ideal building material for nanostructures. It’s easy to churn out in bulk: Kjems and his team hijacked a virus to manufacture copies of the sequence that they designed. And it folds in straightforward, predictable ways according to its sequence. To design the box, the Aarhus team developed a computer program to generate a continuous single-stranded DNA sequence that, along with smaller DNA fragments that act as staples, would self-assemble into the desired shape.

The sequence was devised with many complementary regions so that it would automatically fold into six roughly square accordion-like sheets–the sides of the box–based on DNA’s natural tendency to pair into double strands. The DNA staples, also driven by the pairing of complementary sequences, stitched the sheets’ edges together to form a hollow cube with a hinged lid.

To make the lid lockable, Kjems and his colleagues fashioned two tiny DNA latches with sticky ends. Under normal circumstances, the latches adhere to the box, holding it shut. But when the two corresponding DNA keys are added, the latches bind to those instead, allowing the lid to swing open. A pair of dye molecules, one affixed to the box’s rim and another to its lid, glow red when close together and green when far apart, providing an easy way to detect whether a box is closed or open.

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Credits: : Ebbe S. Andersen, Aarhus University

Tagged: Biomedicine, DNA, drug delivery, nanostructure, origami

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