William Shih has a bridge to sell, but you’ll need a powerful microscope to see it: It’s built entirely from DNA strands, handrails and all.
The bridge is just one of a whole range of intricate three-dimensional shapes Shih has crafted using DNA’s unique capacity for precise self-assembly. In a study Thursday in Science, his team has shown they can even control the precise curvature of these tiny structures, which is key to making wheels, hooks and gears.
Unlike building nano portraits of Obama, This isn’t just an artistic exercise. Scientists in the burgeoning field of structural DNA nanotechnology are exploring DNA’s potential as raw material for next-generation circuits, sensors and biomedical devices. Advocates say it could become the new go-to material for engineers, scientists and clinicians.
“DNA is the world’s greatest architectural material, in my opinion,” said NYU chemist Ned Seeman, the field’s founder and lonely apostle.
In addition to its well-known sequence specificity — A only binds T, G only binds C — DNA’s structural properties have been intensely studied for over half a century, and one can predict the atomic-level structure of virtually any DNA construct with remarkable accuracy. Since the 1980s, Seeman has been quietly designing DNA strands that self-assemble into interlocking tiles, three-dimensional polyhedrons and even nanomachines that automatically ‘walk’ along other DNA strands.
In 2006, the technology finally entered the scientific limelight, heralded by a Nature cover festooned with cheerful smiley faces, each composed of a long, folded strand of DNA meticulously wrangled into shape with tiny DNA “staples,” a technique that its inventor, CalTech computer scientist Paul Rothemund, termed “DNA origami.”
“There are at least a dozen groups focusing on things [Seeman] invented, and a larger number working on this at the periphery,” said Shih, who is at the Dana-Farber Cancer Institute.
In May, scientists at Copenhagen’s Center for DNA Nanotechnology described a DNA-based box with a lid that stays locked until exposed to a DNA-based key, which prompts the lid to pop open and potentially release a drug. A team led by McGill University chemist Hanadi Sleiman is also building DNA cages and nanotubes for delivering treatments.
“This might be the kind of thing that comes into cells and only opens up when it’s triggered by a gene that’s overexpressed in very specific cells,” Sleiman said.
But perhaps the field’s greatest promise is in using DNA as a foundation for more sophisticated devices.
Because complementary DNA sequences recognize each other, short DNA strands can act as “address labels” to direct cargos to exact locations on a larger DNA origami scaffold. Tagged proteins, chemical compounds and even nanoscale electronic components are able to find and claim their proper positions with atomic-scale precision to form complex molecular machines that essentially build themselves.
In the latest study, Shih’s team created curves in DNA structures by adding or deleting DNA base pairs to create tension that causes the strands to bend.
“DNA structures are the ’smart’ materials which we use to assemble ‘dumb’ materials, but these dumb materials can have other interesting properties,” said Duke University chemist/computer scientist Thom LaBean, who is currently working on tiny DNA-templated wires and single-electron transistors that could convert DNA scaffolds into nanoscale circuitboards.
LaBean is also working on ‘biocomputers’ made from DNA, RNA and protein that respond to biological signals. For example, A DNA-based sensor that recognizes RNA messages produced because of cancer or viral infection could trigger the release of RNA or DNA strands with therapeutic properties.
Such applications should benefit considerably from the new three dimensional opportunities.
“Distances can be shorter, and you can get a lot more stuff into 3D than 2D,” Seeman said. “Ultimately, self-assembly in 3D will enable things that self-assembly in 2D won’t.”
One possibility, being developed by Sleiman, is a DNA solar cell that incorporates metal atoms and other chemical components to mimic the efficient mechanisms bacteria use to derive energy from the sun.
“Nature just positions all these different functional elements exactly right in three-dimensional space in order to create this bacterial photosynthesis machine,” she said. “And no self-assembling system can rival what DNA can do in terms of positioning.”
There are of course obstacles, such as finding cheaper ways to produce bulk quantities of DNA, optimizing the design and construction process, and demonstrating safety in humans.
Even more fundamental are the matters of convincing a skeptical scientific community and acquiring funding. Recruiting people who can wrap their heads around such highly interdisciplinary work, which brings together elements of biology, physics, chemistry, computer science and materials, is also a challenge.
On the other hand, the inherent sexiness of DNA nanotechnology makes it an easy sell for prestigious journals like Science and Nature, and most practitioners seem optimistic that the scientific community will ultimately recognize the power of structural DNA nanotech.
“I think the general idea of being able to control the fine structure of matter… could potentially affect a lot of areas of technological interest,” Shih said. “We need some more killer applications, and then we’ll punch through the threshold, and there will be more general appreciation for this field.”
Image: Science/AAAS
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