The DNA box is the largest and most complex artificial self-assembled structure reported to date, explains Jorgen Kjems of Aarhus University. It is also the smallest box ever made.

The DNA origami method was developed by Paul Rothemund of Caltech in 2006 and was originally used to construct 2D DNA structures. Origami is the Japanese word for paper folding and in the DNA technique a large viral genome is folded by hybridizing more than 200 small synthetic DNA sequences. Kjems and colleagues have now extended this technique by developing software that can fold any 2D nanostructure, and recently also 3D structures.

The box is large enough to hold a single ribosome or poliovirus and its six faces are formed from parallel, interlinked DNA helices folded into shape thanks to 220 short synthetic nucleus strands (or oligonucleotides).

The lid of the box closes when two DNA sequences in the lid recognize two complementary sequences inside the box. The two DNA helices that subsequently form close the box.

However, something else can happen too: two specific external RNA or DNA sequences can form longer helices with the two DNA locks inside the box. These two external sequences "out compete" the helices inside the locks and release the lid. "The lid will then automatically open thanks to repulsion between all of the negative charges in the box," Kjems told

As well as being able to carry and deliver drugs inside cells, the box might also act as an amplifier. This is because the presence of only two DNA molecules can lead to the release of a large number of reporter compounds inside the box, says Kjems. It could thus be used to develop a new type of biosensor.

The team, which includes researchers from the Max Planck Institute for Biological Chemistry and the University of Göttingen, both in Germany, will now test drug delivery inside cells using the nano-box.

The work was reported in Nature.