A video from Harvard's Wyss Institute explains how strands of DNA can be assembled into three-dimensional nanostructures like tiny Lego building blocks.

By Alan Boyle

Researchers at Harvard's Wyss Institute have coaxed single strands of DNA to fit together like Lego bricks and form scores of complex three-dimensional shapes, including a teeny-tiny space shuttle. The technique, described in this week's issue of the journal Science, adds a new dimension to molecular construction and should help open the way for nanoscale medical and electronic devices.

"This is a simple, versatile and robust method," the study's senior author, Peng Yin, said in a news release.

The method starts with synthetic strands of DNA that take in just 32 nucleotides, or molecularbits of genetic code. These individual "bricks" are coded in a way that they fit together like Lego pegs and holes to form larger shapes of a specific design. A cube built up from 1,000 such bricks (10 by 10 by 10) measures just 25 nanometers in width. That's thousands of times smaller than the diameter of a single human hair.

The latest research builds upon work that the Wyss researchers detailed in May, which involved piecing together DNA strands to create two-dimensional tiles (including cute smiley faces). This time around, the strands were twisted in such a way that they could be interlocked, Lego-style. As any visitor to Legoland knows, such structures can get incredibly complex in the hands of a skilled builder.

Yin and his colleagues are still learning their building techniques. Fortunately, the bricks could be programmed to build themselves, with the aid of 3-D modeling software. Once the designs were set, the researchers synthesized strands with the right combinations of nucleotides adenosine, thymine, cytosine and guanine so that when they were mixed together in a solution, at least some of the bricks would form the desired design.

To demonstrate the method, 102 different 3-D shapes were created using a 1,000-brick template.

The Wyss researchers reported a wide variation in assembly success rate, or yield: Depending on the design, the yield ranged from 1 percent to 40 percent.That's roughly in the same range as the success rate for another method for molecular assembly, known as DNA origami. The origami method requires more custom work to design the "staples" to hold the DNA structures together, while the Lego-style method can rely more easily on a standard toolbox of DNA bricks.

In the future, DNA origami and DNA brick-building may be used together, said Kurt Gothelf, director of the Center for DNA Nanotechnology at Aarhus University in Denmark. "It is likely that a combination of the two methods will pave the way for making even larger structures in higher yields," Gothelf wrote in a commentary for Science.

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Scientists build with tiny bricks of DNA