Researchers can use software to create tiny rounded objects from DNA. Here’s why that’s cool

Admire the tiny nanostructures being created in the research labs at Duke University and Arizona State University, and it’s easy to imagine yourself browsing a catalog of the world’s smallest pottery.

A new paper reveals some of the teams’ creations: tiny vases, bowls and hollow spheres tucked one inside the other, like household goods for a Russian nesting doll.

But instead of making them out of wood or clay, the researchers designed these objects from threadlike DNA molecules that were bent and folded into complex three-dimensional objects with nanometer precision.

These creations demonstrate the possibilities of a new open source software program developed by Duke Ph.D. was developed. Student Dan Fu with his advisor John Reif. Described in diary on December 23 scientific advancesthe software allows users to take drawings or digital models of round shapes and convert them into 3D structures made from DNA.

The DNA nanostructures were assembled and imaged by co-authors Raghu Pradeep Narayanan and Abhay Prasad in Professor Hao Yan’s lab in Arizona. Each tiny hollow object is no more than two-millionths of an inch in diameter. More than 50,000 of them fit on the head of a pin.

But researchers say these are more than just nano-sculptures. The software could allow researchers to create tiny containers for drug delivery or molds for casting metal nanoparticles with specific shapes for solar cells, medical imaging and other applications.

For most people, DNA is the blueprint of life; the genetic instructions for all living things, from penguins to poplars. But for teams like Reif and Yan, DNA is more than a carrier of genetic information—it’s source code and construction material.

There are four “letters” or bases in the genetic code of DNA that pair up in our cells in predictable ways to form the rungs of the DNA ladder. It’s these strict base-pairing properties of DNA — A with T and C with G — that the researchers have co-opted. By designing strands of DNA with specific sequences, they can “program” the strands to self-assemble into different shapes.

The process involves folding one or a few long pieces of single-stranded DNA, thousands of bases long, with the help of a few hundred short strands of DNA, which bind to complementary sequences on the long strands, “stapling” them in place.

Researchers have been experimenting with DNA as a building material since the 1980s. The first 3D shapes were simple cubes, pyramids, soccer balls – geometric shapes with rough and blocky surfaces. But designing structures with curved surfaces that more closely resemble those found in nature has been difficult. The team’s goal is to expand the range of shapes possible with this method.

For this purpose, Fu developed a software called DNAxiS. The software is based on a method for building with DNA described in 2011 by Yan, who 20 years ago was a postdoc at Reif at Duke before joining the Arizona State faculty. It works by winding a long double helix of DNA into concentric rings that are stacked on top of each other to form the object’s contours, much like using balls of clay to make a pot. To make the structures stronger, the team also made it possible to reinforce them with additional layers for more stability.

Fu shows the variety of shapes they can make: cones, gourds, shamrock shapes. DNAxiS is the first software tool that allows users to automatically design such shapes, using algorithms to determine where to place the short DNA “clips” to join the longer DNA rings together and the shape in place to keep.

“If there are too few or if they are in the wrong position, the structure won’t form properly,” Fu said. “Before our software, the curvature of the shapes made this a particularly difficult problem.”

For example, in a model of a mushroom shape, the computer spits out a list of strands of DNA that would self-assemble in the correct configuration. Once the strands are synthesized and mixed in a test tube, the rest takes care of itself: By heating and cooling the DNA mixture in just 12 hours, it “magically folds into the DNA nanostructure,” Reif said.

The researchers said the practical applications of their DNA design software in the laboratory or clinic could be years away. But “it’s a big step forward in terms of the automated design of novel three-dimensional structures,” Reif said.