Scientists smiled with DNA origami

Ten years ago, Caltech scientist Paul W. K. Rothemund published the first paper on DNA origami. He demonstrated that one long single strand of DNA could fold into a predetermined shape of double-stranded DNA when it encounters many short single strands of the nucleic acid.

Scientists had previously used DNA to build cubes and other simple geometric shapes. But Rothemund took DNA construction to a new level of complexity, crafting two-dimensional smiley faces, snowflakes, and a map of the Americas just 100 nm across. The work charmed scientists, and Rothemund’s DNA smiley face was featured on the cover of Nature, blown up and colored a cheerful yellow (Nature 2006, DOI: 10.1038/nature04586).

In the intervening years, Rothemund says, the number of people working in the field of DNA origami has grown quickly. Other groups have made more complicated 2-D shapes as well as 3-D shapes, and even DNA origami “nanobots” that change shape in the presence of certain cancer cells. Despite the progress, Rothemund adds, DNA origami has been slow to gain traction among those researchers who might use it practically in areas such as photonics or electronics, for example, to position molecules on semiconductor surfaces.

This year, Rothemund’s group reported using DNA origami to reproduce a dime-sized version of Van Gogh’s painting “The Starry Night.” The DNA folded into photonic crystal cavities tuned so that fluorescent molecules would glow red when installed into the spaces (Nature 2016, DOI: 10.1038/nature18287). “We’re slowly trying to convince physicists that it’s really worthwhile,” Rothemund says.

Hendrik Dietz, now a biophysics professor at the Technical University of Munich, remembers reading Rothemund’s landmark Nature paper when it came out in 2006. At the time, Dietz was a graduate student at TUM working in the area of single-molecule biophysics, and he’d taken the journal to the gym to read it while running on the treadmill. Dietz had been considering changing fields, and after learning about DNA origami, he had found his new calling.

“Ten years ago, people considered DNA origami to be a curiosity—just a way to make funny shapes,” Dietz says. But in the intervening decade he thinks it has become more useful, even if it has primarily been in niche applications, such as precision measurements of biomolecules. For example, Dietz’s group recently used DNA origami to study the stacking forces in DNA (Science 2016, DOI: 10.1126/science.aaf5508).

Although DNA origami has yet to find a killer app, Dietz thinks the technique has already delivered on its promise. “Through the efforts of making increasingly more complex objects, we have learned so much about the molecule DNA,” he says. “I don’t really see how you would have gained that understanding—the thermodynamics, the mechanics, the kinetics—without trying to build something with the molecule. This in itself is of great value.”