Researchers design 3D DNA structures

Marvel at the tiny nanoscale structures emerging from the research labs of Duke University and Arizona State University, and it’s easy to imagine you’re browsing through a catalog of the most small pottery of the world.

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

But instead of making them from wood or clay, the researchers crafted these objects from threadlike DNA molecules, bent and bent into complex three-dimensional objects with nanoscale precision.

These creations demonstrate the possibilities of new open-source software developed by Duke Ph.D. student Dan Fu with his advisor John Reif. Described Dec. 23 in the journal Science Advances, the software allows users to take drawings or digital models of rounded shapes and turn them into 3D structures made of DNA.

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

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

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

There are four “letters,” or bases, in the genetic code of DNA, which come together in predictable ways in our cells to form the rungs of the DNA ladder. It is these strict base-pairing properties of DNA – A with T and C with G – that the researchers co-opted. By designing strands of DNA with specific sequences, they can “program” the strands to reassemble into different shapes.

The method involves refolding one or a few long pieces of single-stranded DNA, thousands of bases in length, using a few hundred short strands of DNA that bind to complementary sequences on the long strands and ” staple” 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, blocky surfaces. But designing structures with curved surfaces closer to those found in nature has been tricky. The team’s goal is to expand the range of shapes possible with this method.

To do this, Fu developed software called DNAxiS. The software builds on a DNA construction method described in 2011 by Yan, who was a postdoc with Reif at Duke 20 years ago before joining the faculty at Arizona State. It works by winding a long double helix of DNA into concentric rings that stack on top of each other to form the outlines of the object, like using coils of clay to make a pot. To make the structures stronger, the team also made it possible to reinforce them with additional layers for added stability.

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

If there are too few or they are in the wrong position, the structure will not form properly. Before our software, the curvature of shapes made this a particularly difficult problem. »

Daniel Fu, Duke Ph.D. student

Given a mushroom-shaped template, for example, the computer spits out a list of DNA strands that would self-assemble into 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 as little as 12 hours “it magically folds into the DNA nanostructure,” Reif said.

Practical applications of their DNA design software in the lab or clinic could still take years, the researchers said. But “it’s a big step forward in terms of the automated design of new three-dimensional structures,” Reif said.

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