DNA nanotechnology uses the unique physical properties of DNA molecules to design and create nanoscale structures, with the hope of one day creating tiny machines that work together just like the parts of a cell. But one of the challenges of the field is to find ways to design and engineer DNA structures with high precision. A recent study published in Science marks a breakthrough in researchers’ ability to shape DNA; it describes a way to build three-dimensional DNA shapes with elaborate twists and curves with unprecedented precision, developed by scientists at Harvard and the Technical University of Munich in Germany.
Fixed gear: A new method for designing three-dimensional shapes from DNA makes it possible to create curved parts, including this nanoscale “gear” with twelve teeth.
Hao Yan, a biochemistry professor at Arizona State University who was not involved in the study, says that the work adds a key level of control over previous methods. “I think we can say that it is possible to create any kind of architecture using DNA,” he says.
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A key advantage of using DNA as a construction material is that it is programmable. DNA molecules consist of strings of linked nucleotide bases of four types: A, T, G, and C. These bases stick to the bases on another DNA strand following a simple rule: A pairs with T, and C pairs with G. By creating DNA sequences with complementary bases on different strands, it is therefore possible to design DNA molecules that self-assemble into certain shapes according to predictable rules.
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Previous work used a method called “DNA origami” to design two-dimensional shapes from DNA; further studies have built upon this approach to create shapes in three dimensions. DNA origami uses one very long strand of DNA, called the scaffold, and hundreds of shorter strands, called staples. The staples bind to the scaffold at certain sites based on their sequence, pinching the scaffold and forcing it to double back many times over to create a sheet in a particular shape.
The Science study extends work by the same team of researchers, adapting the DNA origami method to create more-complex three-dimensional shapes. Previously, the team designed DNA to form helices bundled by cross-linked staple strands in a honeycomb-like lattice. In the current study, the researchers introduced bends and twists into these shapes by adding or deleting bases at certain points in the scaffold, changing the local forces that the helices exert on one another and forcing the entire structure to curve to the right or left. They found that they could control the degree of curvature with a great deal of precision, achieving sharp bends similar to those of the tightly wound DNA found in cells.
The researchers created objects including nanoscale “gears,” a wireframe beach ball-shaped capsule, and triangles with either concave or convex sides. Shawn Douglas, a co-author at Harvard University, developed a publicly available computer-aided design program that can serve as a visual interface for designing the DNA shapes.
Bendable molecules: A bundle of DNA helices (top row) can be made to bend at precise angles (the other rows) by introducing or deleting base pairs in the DNA sequence.
William Shih, a co-author of the study and assistant professor of biological chemistry and molecular pharmacology Harvard Medical School, says that the ability to make curved structures adds an important element to the DNA nanoscience toolbox. He points out that objects like rings, springs, and gears are important for machines at the macroscale, while cells also contain elements with curved parts, suggesting that these properties are important on the nanoscale. “If we didn’t have this general building capability, we would be handicapped in our ability to build useful devices,” he says.
Chengde Mao, an associate professor in analytical chemistry at Purdue University, calls the achievement “surprising” and says that his own lab has attempted to make similar structures and failed. He says not only that the work shows that DNA can be twisted and bent to extreme degrees but that “one of the nice things is that it’s a really smooth curve,” whereas other attempts have resulted in shapes that are pixilated.
The practical applications of the technique are still unclear, but there are many possibilities. Since the DNA shapes described in the Science paper are the size of an average virus, Shih says they could perhaps be designed to enter a cell like a virus in order to release a drug. DNA parts might also be used to design molecular electronics, which could someday offer a new level of miniaturization for faster computers.
Yan says that the study adds to the impressive abilities of DNA, but adds that scientists need to study these structures further to see how stable they are and how well they hold up over time.
