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DNA designs done faster, cheaper

B. Wei et al. / Wyss Institute, Harvard

This atomic-force microscopy shows 100 shapes, each created from tiles of DNA strands. Each shape takes up a space measuring 150 by 150 nanometers, or roughly one-thousandth the width of a human hair.

The DNA molecule serves as the code of life, but it also serves as handy building material for nanoscale structures — and newly published research shows how patterns as complex as letters, numbers and smiley faces can be created far more cheaply and quickly than previously thought.

Harvard researchers demonstrate the latest twists in this week's issue of the journal Nature. The process involves laying out short segments of DNA in a tile-shaped pattern determined by custom-designed chemical bonds. Those single-stranded tiles, in turn, can assemble themselves into larger shapes like Lego blocks, depending on how the bonds attach to one another. Different recipes for mixing the tiles together will produce different shapes.

The researchers — Bryan Wei, Mingjie Dai and Peng Yin — estimate that the process yielded the desired structure 12 to 17 percent of the time. That yield is far from perfect, but it could be perfectly acceptable for a process involving thousands upon thousands of self-assembling molecules.

The technique updates a construction strategy that was first pioneered in the 1980s. Back then, it took two years to create a 7-nanometer-wide cube from 10 strands of DNA, Caltech's Paul Rothemund and Aarhus University's Ebbe Sloth Andersen observed in a Nature commentary on the research. In contrast, the newly reported results suggest that far more complex shapes, measuring more than 100 nanometers across, could be churned out at an average rate of one per hour. (A human hair is roughly 100,000 nanometers wide.)

Another attractive factor has to do with the cost: An alternate method for creating nanoscale shapes, known as DNA origami, twists one long molecular strand into a desired shape rather than using lots of smaller tiles. But for each different shape, a new set of molecular "staples" has to be synthesized at a cost of roughly $1,000, according to the Nature commentary. The Harvard researchers' method involves creating a $7,000 set of tiles that could theoretically produce 2 X 10^93 shapes. That's a 2 followed by 93 zeros.

In their Nature paper, Wei and his colleagues showed off 100 shapes — including the Roman alphabet, numerical digits, punctuation marks, the peace sign, Chinese characters and 10 kinds of emoticons. They made use of a custom-designed computer program to aid in the design of the shapes and control the liquid-handling robot that mixed the DNA ingredients.

"This advance truly brings DNA nanotechnology into the rapid-prototyping age, and enables DNA shapes to be tailored for every experiment," Rothemund and Andersen wrote in their commentary.

One of the puzzles surrounding the research has to do with why it works so well. Experts had thought that when smaller strands of DNA were mixed together, they wouldn't come together correctly and completely to form the desired larger shapes. The authors suggested that the timing of the chemical reactions could be the key to their success. "It is conceivable that sparse and slow nucleation followed by fast growth allows complete assembly," they wrote.

Nature News quoted Yin as saying that "any technological applications are highly speculative" — but if the process can be extended to a mirror-image type of DNA that isn't broken down by cellular processes, it could lead to the development of nanoscale devices for drug delivery or molecular-scale medical monitoring. The researchers say they're in the midst of obtaining a provisional patent for the process.

In their commentary, Rothemund and Andersen compared DNA assembly to carpentry.

"Wei and colleagues' findings remind us that we are still just apprentice DNA carpenters, and will embolden others to mix hundreds of DNA strands together against prevailing wisdom," they wrote. "The results will probably surprise us."

More about molecular carpentry:

The research reported in Nature, "Complex Shapes Self-Assembled From Single-Stranded DNA Tiles," was funded by the Office of Naval Research, the National Science Foundation, the National Institutes of Health and Harvard's Wyss Institute for Biologically Inspired Engineering.

Alan Boyle is msnbc.com's science editor. Connect with the Cosmic Log community by "liking" the log's Facebook page, following @b0yle on Twitter and adding the Cosmic Log page to your Google+ presence. You can also check out "The Case for Pluto," my book about the controversial dwarf planet and the search for new worlds.