Scientists mold DNA into donuts, teddy bears and an image of the Mona Lisa | Science



New DNA origami techniques can build objects the size of viruses in virtually any way.

Wyss Institute

Scientists have made a breakthrough in building shapes from the so-called building blocks of life. The new techniques can shape DNA, the double-stranded helical molecule that encodes genes, into objects up to 20 times larger than those previously achieved, three separate groups report today. Together, the new approaches can make objects of virtually any shape: 3D donuts and dodecahedrons, cubes with cut-outs in the shape of a teddy bear, and even a mosaic image of the Mona Lisa . The techniques could one day lead to a large number of novel devices for electronics, photonics, nanoscale machines and possibly disease detection.

Scientists have been making forms of DNA since the 1980s, and those efforts took off in 2006 with the invention of a folding technique called DNA origami. It begins with a long chain of DNA, called scaffolding, which has an exact sequence of the four molecular units, or nucleotides, called A, C, G and T, with which DNA spells its genetic code. Researchers link scaffold patches with complementary strands of DNA called staples, which attach to their targets in two separate places. By connecting these patches, the scaffolding is folded in a prescribed manner. A second version of the technology, introduced in 2012, uses only small strings of DNA, but not scaffolds, which are assembled into Lego-like bricks that can then be joined.

Both approaches have been very popular among nanotechnologists, allowing them to design made-for-DNA forms from the bottom up. Researchers have also been able to coat their DNA objects with plastics, metals and other materials to create small components of machines, electronic products and photonic devices. But the size of conventional DNA objects has been limited to about 100 nanometers: make them grow more and become too flexible to adopt a particular shape or can not make the necessary connections with their neighbors to grow.

Not anymore. Groups in Germany, Massachusetts and California report today in Nature that they have manufactured DNA objects with a newly discovered weight. The German team, led by Hendrik Dietz, a biophysicist at the Technical University of Munich, modified the traditional approach to origami, using it to create rigid DNA modules with preprogrammed forms that can be assembled with other copies to build specific shapes. For example, in solution, the DNA strands designed to bend into 3D wedges combine with each other to form a miniature donut about 300 nanometers in diameter. And the modules that form three-pronged vertices are assembled into several objects, including dodecahedrons that are 440 nanometers wide.

The Massachusetts team, led by Peng Yin, a systems biologist at the Wyss Institute at Harvard University in Boston, modified the DNA brick approach. that they invented, to make bigger and more complex structures. In the original technique, each Lego-like brick has a DNA "linker" eight nucleotides long that blocks it in place with its neighbors. The new approach uses links of 13 nucleotides each. In their article, Yin and his colleagues explain how to create a block consisting of 33,000 bricks and 1.7 million DNA nucleotides. By omitting bricks in the center of these blocks, they also created cutouts in the shape of everything, from an hourglass to a teddy bear. Although these empty structures are not yet useful, the technique "gives us the ability to design highly complex systems," says Yin.

New DNA origami techniques can make objects much larger, like this dodecahedron composed of 1.8 million bases of DNA.

K. WAGENBAUER ET AL ., NATURE VOL. 551, 2017

The third group, led by Lulu Qian, a biochemist at the California Institute of Technology in Pasadena, devised a new way to create flat images of origami DNA. Using a multi-stage assembly process, the researchers created origami-based pixels that appear in different shades when viewed with a device called an atomic force microscope. They gathered dozens of pixels in individual arrangements. Then they wove together 64 separate matrices to render an image of the [MonaLisa composed of more than 8700 pixels measuring 0.5 micrometers on one side.

Researchers have previously shown that they can decorate smaller DNA creations with everything from nanoscale metal particles to fluorescent chemical compounds, which may one day be useful for making new electronic and photonic devices. Because the larger DNA origami gives researchers more space to sculpt, it opens the door to creating increasingly complex templates for coatings, says Yin. "We are taking a collective leap in terms of the scale and usefulness of these systems," he says.

It's only a matter of time before the objects get bigger. The Yin group stopped cultivating its structures not so much because of technical limitations, but because of the high cost of synthesizing all the DNA, which can cost more than $ 100,000 per gram. However, another technique by Dietz and his colleagues, also published today in Nature could reduce that cost barrier. The researchers created thousands of custom-made DNA strands while persuading viruses to replicate the filaments within bacterial hosts, they reported. Similar to how biotechnology experts generate large amounts of genetically modified proteins for drugs, this batch method could reduce the cost of DNA synthesis to approximately $ 200 per gram, says Dietz.

Together, the new approaches "unlock the potential for application of origami DNA," says Carlos Castro, an expert in DNA nanotechnology at Ohio State University in Columbus. Other researchers have already loaded origami hollow structures with drugs to attack specific types of cancer cells, created "robots" of DNA that cross surfaces and mimic the shape of viruses. But because the new DNA objects are on the same scale as devices that can be modeled using computer chip lithography, it might be possible to integrate the two technologies and design DNA origami to detect cancer biomarkers and other biological targets that could then read by electronic devices, says Castro. And that's just a possible set of devices. Yin adds: "Now, there are so many ways to be creative with these tools"

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