Swan in a Box

Swan in a box
The word origami comes from the Japanese words oru (to fold) and kami (paper). You’ve seen the delicate swans, cranes, flowers, stars, and boxes — each made from a single colorful sheet of paper.

Samurai warriors of old exchanged gifts adorned with noshi, a good luck token made of folded strips of paper. Origami butterflies were used during the celebration of Shinto weddings to represent the bride and groom.

Paper is not the only material that can be used for origami. Paul Rothemund’s seminal 2006 article in Nature shows that stringy DNA molecules can be folded –- not unlike paper cranes –- into tiny, two-dimensional patterns known as DNA origami.

He refers to this as a "bottom-up fabrication" technique that exploits the intrinsic properties of atoms and molecules to make simple nanostructures at a scale of 10-9 meters (one billionth of a meter or a nanometer).

A new article in Nature now announces a further step – the construction of three-dimensional DNA origami “nanoboxes” that can be locked or opened in response to keys made from short strands of DNA. By changing the nature or number of these keys, it’s possible to use the boxes as drug delivery systems, sensors, or even molecular computers.

The implications of this are nothing short of revolutionary – it could mark the beginning of a new era in pharmacology and drug delivery. It may be possible for a DNA origami nanobox to localize certain markers in cancer cells and deliver an anti-cancer drug… at precisely the right spot. This would mitigate the agonizing and adverse effects of chemotherapy.

Led by chemist Jørgen Kjems of Denmark’s Aarhus University, researchers stitched together strands of DNA to form boxes measuring 42x36x36 nanometers that open and close.

Since DNA is formed of molecules that recognize and bind with one another in a deterministic manner, Kjems’ team was able to write a computer program to calculate the geometry of particular sequences of those molecules to make a six-sided, hollow box –- including a lid that opens.

Taking 220 snippits of DNA –- the number determined by the computer algorithm –- and mixing them with a bacteriophage (a long piece of viral DNA), Kjems was able to induce the self-assembly of billions of boxes. “It’s amazing that it works,” Kjems told Nature. “It’s like taking your car apart, putting the nuts and bolts into a bag, shaking it, and the car builds itself.”

Nanotechnology pioneer Eric Drexler comments, “Structures like [the nanobox] are built of the same motifs [as Paul Rothemund’s DNA origami folding] and will afford the same capability, but with attachment points no longer constrained to a plane surface.”

It may be possible for a DNA origami nanobox to localize certain markers in cancer cells and deliver an anti-cancer drug… at precisely the right spot.

Kjems’ team also worked out a way of getting the nanoboxes to open and close. By adding extra sections of DNA, they formed locks on the rim of the box, using DNA strands as keys to spring the locks open and pop the lid. When closed, the box sent a red fluorescence signal; when open, a green signal.

They have already begun to experiment putting a payload inside the boxes, including enzymes and quantum dots. Kjems told Chemistry World, “It’s quite big (about 30nm) inside – it could fit virus particles or quite big enzymes and other macromolecules.” The boxes are theoretically solid enough to prevent large molecules from leaking out and spacious enough to enclose a ribosome or a small virus.

The debilitating pathologies associated with aging include cancer, cardiovascular disease, type II diabetes, and Alzheimer’s disease. Controlled drug release therapies targeted at these fundamental mechanisms of aging will be instrumental in counteracting them.

Yet the controlled release of drugs is only one application. The DNA origami nanoboxes can also be used as tiny sensors –- red or green, closed or open –- to monitor biochemical reactions at the cellular level.

And since logic gates on digital circuits are built from Boolean closed/open logic, the nanoboxes could one day become the basis of nanoscale computers –- computers with the power of today’s supercomputers, but smaller than a dust mote on a paper origami swan.

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