DNA Origami Structures Could Spur Development of Future Medical Devices

Researchers at the National Institute of Standards and Technology (NIST) are working to develop DNA-based nanostructures that could eventually pave the way for a new generation of technologies, including sensors and drug-delivery systems. First developed at the California Institute of Technology, such structures are based on the ability of pairs of DNA molecules to assemble into complex structures.

Known as DNA origami, the technology involves laying down a long thread of DNA and attaching 'staples' composed of complementary strands that bind to make the DNA fold up into various shapes, such as rectangles, squares, and triangles. The shapes serve as a template onto which nanoscale objects such as nanoparticles and quantum dots can be attached using strings of linker molecules. The method is a lot like building with LEGOs, according to NIST researcher Alex Liddle. Some patterns enable the blocks to fit together snugly and stick together strongly and some don't.

The researchers measured how quickly nanoscale structures can be assembled using this technique, how precise the assembly process is, how closely the structures can be spaced, and the strength of the bonds between the nanoparticles and the DNA origami template. They discovered that a simple structure, four quantum dots at the corners of a 70- x 100-nm origami rectangle, takes up to 24 hours to self-assemble with an error rate of about 5%.

Other patterns that placed three and four dots in a line through the middle of the origami template were increasingly error prone. Sheathing the dots in biomaterials, a necessity for attaching them to the template, increases their effective diameter. A wider effective diameter (about 20 nm) limits how closely the dots can be positioned and increases their tendency to interfere with one another during self-assembly, leading to higher error rates and lower bonding strength. This trend was especially pronounced for the four-dot patterns.

"If the technology is actually going to be useful, you have to figure out how well it works," says Liddle. "We have determined what a number of the critical factors are for the specific case of assembling nanostructures using a DNA-origami template and have shown how proper design of the desired nanostructures is essential to achieving good yield, moving, we hope, the technology a step forward."