This relatively simple, inexpensive technique could help researchers easily design and build complex nanoscale technology. Scientists could, for instance, plug a variety of device components onto such DNA origami.
"A physicist, for example, might attach nano-sized semiconductor 'quantum dots' in a pattern that creates a quantum computer. A biologist might use DNA origami to take proteins which normally occur separately in nature, and organize them into a multi-enzyme factory that hands a chemical product from one enzyme machine to the next in the manner of an assembly line," said researcher Paul Rothemund, a senior research fellow in computer science and computation and neural systems at the California Institute of Technology in Pasadena.
The DNA origami technique employs long, single stranded DNA molecules almost as pieces of string. A very long single DNA strand is folded back and forth to fill up the outline for any desired shape. Short DNA molecules stapled onto this long DNA scaffold then hold the folded design in place. The sequence of construction blocks in each staple DNA strand match those making up the bends on the scaffold DNA strand, which means the scaffold and staple DNA strands will automatically assemble themselves into the desired shapes in a single step.
"It's really a simple idea that works very well," said bioengineer Michael Diehl at Rice University in Houston.
The technique can create structures and images up to some 100 nanometers in diameter made of roughly 200 pixels each about 6 nanometers wide. Rothemund and his colleagues now simply design whatever shape they desire -- a process that requires about one day -- and then use a computer program to determine what DNA sequences are needed to create that structure. Synthesizing these sequences demands another week, and mixing the strands takes just a few hours.
"At this point, high-school students could use the design program to create whatever shape they desired,'' Rothemund said. Indeed, biochemist Gerald Joyce at the La Jolla, Calif.-based Scripps Research Institute noted his son has already used this program in a high school chemistry project. "This is almost child's play," Joyce said.
"Ned Seeman at NYU pioneered DNA nanotechnology, which allows us to program DNA to self-assemble into almost any imaginable shape on the nanoscale. Paul's method makes DNA nanotechnology 10 to 100 times easier or less expensive before. This will transform DNA nanotechnology from a novelty approach to a mainstream nanoconstruction tool," said Harvard University biochemist William Shih.
In this research, Rothemund "has scored a few unusual 'firsts' for humanity," said Rothemund's colleague Erik Winfree at Caltech. "In a typical reaction, he can make about 50 billion 'smiley faces.' I think this is the most concentrated happiness ever created.
"But the applications of this technology are likely to be less whimsical," Winfree added. "For example, it can be used as a 'nanobreadboard' for attaching almost arbitrary nanometer-scale components. There are few other ways to obtain such precise control over the arrangement of components at this scale."
"I was really taken with the ease and versatility of the technique. It makes it a lot easier to make nanoscale structures of all different types," said chemist Lloyd Smith at the University of Wisconsin in Madison.
Although Rothemund has so far created two-dimensional structures with his technique, he said creating 3-D assemblies should not be a problem. One biomedical application Rothemund said 3-D DNA origami could have is as cages that sequester enzymes until they are ready for use in activating or deactivating other proteins.
"The reason I didn't make 3D structures is not because that would be hard, but because I don't have the right instruments to image 3-D structure," Rothemund said. "I expect that there will be a whole crop of 3-D structures made by the method in the next year or two."
When it comes to when commercial applications for his technique might appear, "my best guess is that it will be five to 10 years before any DNA-organized devices or circuits are incorporated into actual products," Rothemund said.
Rothemund noted that with future versions of the program, "a design could literally be made in minutes." He published his research in the March 16 issue of the journal Nature.
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