It is known that the primary function of DNA in our body cells is to carry genetic information from one generation to the next. However, some scientists have also predicted that DNA can also be effectively utilized as an ideal building material for nanoscale structures. Such DNA based structures can then have applications in drug delivery systems, biosensors, artificial photosynthesis and more.
Over the past few years, scientists have also tried to build DNA structures on a large scale. Five years ago, a new design strategy called DNA origami was laid out by Caltech computational bioengineer Paul Rothemund which involved the construction of two-dimensional shapes from a DNA strand folded over on itself and secured by short "staple" strands. Few years later, William Shih's lab at Harvard Medical School translated this two dimensional concept to three dimensions. This permitted for the design of complex curved and bent structures that opened new avenues for synthetic biological design at the nanoscale. However, automation of the design process was a major obstacle to these complex designs.
To overcome this hurdle of automation, a team led by biological engineer Mark Bathe at MIT, has developed software that allows easier predictions of the three-dimensional shape that will result from a given DNA template. The software doesn't automate the design process completely but then it makes it considerably easier to design complex 3-D structures."We ultimately seek a design tool where you can start with a picture of the complex three-dimensional shape of interest, and the algorithm searches for optimal sequence combinations," says Bathe, the Samuel A. Goldblith Assistant Professor of Applied Biology. "In order to make this technology for nanoassembly available to the broader community — including biologists, chemists, and materials scientists without expertise in the DNA origami technique — the computational tool needs to be fully automated, with a minimum of human input or intervention."Bathe et al have described this software in detail in the Feb. 25 issue of Nature Methods.
DNA is primarily made up of four nucleotide bases known as A, T, G and C, which make the molecule easy to program. According to nature's rules, A binds only with T, and G only with C. "With DNA, at the small scale, you can program these sequences to self-assemble and fold into a very specific final structure, with separate strands brought together to make larger-scale objects," Bathe says. Rothemund's origami design strategy is based on the idea of getting a long strand of DNA to fold in two dimensions, as if laid on a flat surface. In his paper outlining the method, he utilized a viral genome (approximately 8,000 nucleotides) to create 2-D stars, triangles and smiley faces. That single strand of DNA serves as a "scaffold" for the rest of the structure. Hundreds of shorter strands, each about 20 to 40 bases in length, combine with the scaffold to hold it in its final, folded shape.
Bathe also stated that DNA is better suited to self-assembly than proteins since physical properties of proteins are difficult to control and that they are sensitive to their environment. His new software program interfaces with another software program from Shih's lab called caDNAno. caDNAno allows users to create scaffolded DNA origami from a two-dimensional layout manually. According to Rothemund, the CanDo program should allow DNA origami designers to more thoroughly test their DNA structures and tweak them to fold correctly. "While we have been able to design the shape of things, we have had no tools to easily design and analyze the stresses and strains in those shapes or to design them for specific purposes," he says. At the molecular-level, stress in the double helix of DNA decreases the folding stability of the structure and introduces local defects, both of which have hampered progress in the scaffolded DNA origami field.
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