Harvard scientists build tiny structures with DNA Legos

courtesy of Yonggang Ke
courtesy of Yonggang Ke
Tiny, nanoscale DNA structures assembled from DNA bricks. Each brick is a short, synthetic single strand of DNA.

Engineers have found a new and unexpected use for the code of life—as a commonplace building material that can be used to fashion precise 3D structures, ranging from miniature smiley faces to cubes.

Most people think of DNA as the master blueprint that is carried in every cell, spelling out the essential traits of organisms. DNA is the “building block of life” only in the metaphorical sense. But scientists at the Wyss Institute for Biologically Inspired Engineering at Harvard University saw in the material an unexploited versatility, if it were to be used as a real brick. They described Thursday in the journal Science an array of molecular Legos that could one day provide a useful scaffold for building tiny electronic circuits and drug-delivery devices.

To show just how much control they had over structures made of DNA, the team of researchers built a demonstration set of 100 figures. Those ranged from practical engineering feats, such as joining together two structures with a narrow connection, to the whimsical—the alphabet, or a heart.

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When Hendrik Dietz, who leads the Laboratory for Biomolecular Nanotechnology at Technische Universität München in Germany, received a copy of the paper from a colleague at Harvard a few weeks ago, he was full of enthusiasm for the work. It represents a new level of control over building precisely tailored objects at the tiniest scales, he wrote in an e-mail. But Dietz said he also had an almost instantaneous emotional response.

“The 3D thing is so awesome,” he wrote to his colleague. “I almost got tears in my eyes because of the joy. I love the Lego figures. When looking at this, one cannot help but submit to the power of DNA.”

Peng Yin, a core faculty member of the Wyss Institute who led the research, said it was helpful for the researchers to think of the DNA as Lego bricks rather than as molecules. The code of DNA involves four letters—C, G, T, and A—which abide by precise pairing rules: “A” matches up with “T,” and “C” with “G.” To build the structures, researchers started with short strands of DNA, each carrying eight-letter fragments that acted like the prongs on a Lego block. Each eight-letter fragment was like a Lego prong that would only fit one other predetermined Lego.

But unlike a kit that keeps kids busy for hours, these DNA structures required little assembly, once the structures had been designed, Yin said.

“You just add some water and salt and increase the temperature to 90 degrees and let it cool down gradually over three days—that’s it,” Yin said. “In one test tube, there are billions of copies of these individual objects, but they all look the same.”

The work, he said, demonstrates that DNA, essential for life, can have other uses. It builds on earlier research, in which Yin’s team found it could stack DNA bricks on one another in two dimensions. And earlier this year, Yin’s colleague at Harvard, George Church, showed that it was possible to turn DNA into a more conventional storage material. He took the text of his 284-page book, “Regenesis: How Synthetic Biology Will Reinvent Nature and Ourselves,” translated its words into binary code—words became a string of 0’s and 1’s. Then, they translated that binary into the letters of DNA, with A’s and C’s corresponding to 0 and G’s and T’s indicating a 1. They then they created 55,000 short strands of DNA that, read together and properly decoded, amounted to a genetic copy of the book.

Church, who is collaborating with Yin, said the new work would be helpful in any application in which precision was important.

“If you look at the electronics industry, it’s getting smaller and smaller,” Church said, and molecular computing and electronics will enable the next generation of even smaller chips. He noted that one powerful use of the technique would be to attach different materials involved in electronics or circuits to the DNA so they could be towed into the right place to create a tiny device that could be used, for example, in the body.

“It’s a terrific scaffolding, which is not at all what nature intended it to be,” Church said.