Published online 6 May 2009 | Nature | doi:10.1038/news.2009.449

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DNA twisted into boxes

Molecular keys can open tiny containers.

DNA cubeThe boxes are formed from a single strand of DNA.Ebbe Sloth Andersen

A multidisciplinary team of researchers has created tiny DNA strongboxes measuring just 30 nanometres on each side1. The boxes, which can be unlocked with a gene 'key', could be used for drug delivery or as sensors.

The boxes are the latest novelty to emerge from 'DNA origami', the technique by which researchers build structures out of DNA. They use oligonucleotides, short snippets of nucleic acid bearing genetic information, to fold longer strands of DNA into a complex structure. Each box is large enough to hold a single ribosome — the cell's machine for making proteins. Previously, researchers have built tubes and even a map of the Americas using the technique2,3.

The latest work uses the same principle. It's just a little more complicated, according to team member Jørgen Kjems, a chemist at Aarhus University in Denmark. First, researchers wrote a computer program that would determine what genetic sequences were needed to make their box. The program begins with a digital model of a very long strand of DNA from a phage — a virus that infects bacteria. Then, given the shape the researchers want to create, it selects some 250 oligonucleotides that will attach to the DNA and assemble it into the desired form.

That was the hard part. Once the computer had worked out the parts researchers needed, they simply bought the oligonucleotides from suppliers and mixed them with the long DNA strands. The snippets went to work, weaving each strand into six walls and then stitching the walls together. It takes only an hour or two for billions of boxes to form by themselves. "It's amazing that it works," says Kjems. "It's like taking your car apart, putting the nuts and bolts into a bag, shaking it, and the car builds itself."

Sealing the deal

The team could even 'lock' the little boxes using DNA. A short sequence attached to one side of the box would cause it to unstitch and open in the presence of another short DNA 'key' sequence. Kjem says the group could attach up to eight different locks on each box, and that could allow them to be used as sensors for the DNA keys. The work appears today in Nature1.

Cryo-EM picture of DNA cubeImages of the cubes obtained by cyro-electron microscopy.Ebbe Sloth Andersen

"The latch-key system represents a solid proof of principle," says William Shih, a chemist at Harvard University. Shih, who has previously synthesized origami tubes of DNA, says that the new system may be used for drug delivery. Tiny molecules of drugs or other therapeutic substances could be released when a specific genetic marker was present.

That would work only if the boxes were truly locked, adds Paul Rothemund, a researcher at the California Institute of Technology at Pasadena. "Whether or not the 'seal' of the lid of the box is tight is a really important question that has not been answered yet," he says. Questions also remain about how the boxes might react inside the body, and how long they could last there.

Nevertheless, Rothemund and Shih agree that the boxes are an important step forward. Kjems adds that they may be just the beginning. The computer program used in the study should allow researchers to make nearly any structure they can imagine out of DNA, he says. "Now is really the time to start to think, what can you use it for?" 

  • References

    1. Andersen, E. S. et al. Nature 459, 73–76 (2009). | Article |
    2. Douglas, S.M., Chou, J. J. & Shih, W. M. Proc. Natl Acad. Sci. USA 104, 6644–6648 (2007). | Article | PubMed | ChemPort |
    3. Rothemund, P. W. K. Nature 440, 297–302 (2006). | Article | ChemPort |
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