The software allows researchers to create small, round organisms from DNA. Here’s why that’s awesome

No bigger than a virus, each of these nanostructures is built using new software that lets researchers design objects out of concentric rings of DNA. Models are shown (top) along with electron microscopy images of actual objects (bottom). Credit: Raghu Pradeep Narayanan and Abhay Prasad, Yan Lab, Arizona State University.

Marvel at the tiny nanostructures emerging from the research laboratories at Duke University and ASU, and it’s easy to imagine browsing through the catalog of the world’s smallest pottery.

A new paper reveals some of the team’s creations: small vases, bowls, and pompoms, one hidden inside the other, like the household items of a Russian nesting doll.

But instead of making them out of wood or clay, the researchers fashioned these from strand-like molecules of DNA, bending and wrapping them into complex 3D objects with nanometer precision.

These creations demonstrate the capabilities of a new, open source program developed by Duke Ph.D. Student Dan Foo with advisor John Reeve. Described on December 23 in the journal Science advancesThe software allows users to take digital drawings or models of rounded shapes and convert them into 3D structures made of DNA.

DNA nanostructures were assembled and imaged by co-authors Raghu Pradeep Narayanan and Abhay Prasad in the lab of Professor Hao Yan at Arizona State. Each small hollow object is no more than two million inches wide. More than 50,000 of them can fit a pin header.

But the researchers say these are more than just nanosculptures. The software could allow researchers to create small drug-delivery containers, 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, DNA is more than just a vector of genetic information—it’s the source code and building material.

There are four “letters,” or bases, in the genetic code of DNA, which pair in a predictable way in our cells to form the rungs of the DNA ladder. It’s the strict base-pairing properties of DNA — A with T and C with G — that the researchers chose. By designing strands of DNA with specific sequences, they can “program” the strands to put themselves together into different shapes.

The method involves folding one or a few long pieces of single-stranded DNA, thousands of bases in length, with the help of a few hundred short DNA strands that attach complementary sequences onto the long strands and ‘staple’ them into place.

Researchers have experimented with DNA as a building material since the 1980s. The first three-dimensional figures were simple cubes, pyramids and soccer balls – geometric shapes with rough surfaces and mass. But designing structures with curved surfaces closer to those found in nature has been challenging. The team’s goal is to broaden the range of possible shapes in this way.

To do this, Fu has developed software called DNAxiS. The program is based on a method for building with DNA, described in 2011 by Yan, who was a postdoctoral researcher with Reeve at Duke University 20 years ago before joining the faculty at Arizona State. It works by wrapping a long double helix of DNA into concentric rings that stack on top of each other to form the contours of the body, much like using coils of clay to make a pot. To make the structures stronger, the team also made it possible for them to be reinforced with additional layers to increase stability.

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

“If there are too few, or if they are in the wrong position, the structure will not form properly,” Fu said. “Prior to our program, the curvature of shapes made this a particularly difficult problem.”

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

The researchers said practical applications of their DNA design software in the laboratory or clinic may still be years away. “It’s a huge step forward in terms of the automated design of new 3D structures,” Reeve said.

more information:
Daniel Fu et al., Automated design of 3D DNA origami with non-point 2D curvature, Science advances (2022). DOI: 10.1126/sciadv.ade4455.

Provided by Duke University

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