DNA-Based Robot Could Eventually Find Use in Therapeutic Devices

A team of scientists has programmed an autonomous molecular "robot" made out of DNA to start, move, turn, and stop while following a DNA track. This technology could eventually lead to molecular systems that might one day be used for medical therapeutic devices and molecular-scale reconfigurable robots. A paper describing this work appears in the journal Nature.

Shrinking robots down to the molecular scale would provide the same kinds of benefits that classical robotics and automation provide at the macroscopic scale. In theory, molecular robots could be programmed to sense the presence of disease markers on a cell, decide to neutralize the diseased cell, and deliver drugs. The power of robotics lies in the fact that once programmed, the robots can carry out their tasks autonomously, without further human intervention.

"In normal robotics, the robot itself contains the knowledge about the commands, but with individual molecules, you can't store that amount of information, so the idea instead is to store information on the commands on the outside," says Nils Walter, professor of chemistry and director of the Single Molecule Analysis in Real-Time (SMART) Center at the University of Michigan (Ann Arbor).

"We were able to create such a programmed or 'prescribed' environment using DNA origami," explains Hao Yan, professor of chemistry and biochemistry at Arizona State University (Tempe). DNA origami is a type of self-assembled structure made from DNA that can be programmed to form nearly limitless shapes and patterns. Exploiting the sequence-recognition properties of DNA base pairing, DNA origami is created from a long single strand of DNA and a mixture of different short synthetic DNA strands that bind to and "staple" the long DNA into the desired shape. The origami used in the Nature study was a rectangle roughly 2 nm thick and 100 nm long.

The researchers constructed a trail of molecular "bread crumbs" on the DNA origami track by stringing additional single-stranded DNA molecules, or oligonucleotides, off the ends of the staples. These represent the cues that tell the molecular robots what to do.

To build the 4-nm-diameter molecular robot, the researchers started with a common protein called streptavidin, which has four symmetrically placed binding pockets for a chemical moiety called biotin. Each robot leg is a short biotin-labeled strand of DNA, "so this way we can bind up to four legs to the body of our robot," Walter says.

"It's a four-legged spider," notes Milan N. Stojanovic, a faculty member in the division of experimental therapeutics at Columbia University (New York City). Three of the legs are made of enzymatic DNA, which is DNA that binds to and cuts a particular sequence of DNA. The spider also is outfitted with a "start strand"--the fourth leg--that tethers the spider to the start site (one particular oligonucleotide on the DNA origami track). "After the robot is released from its start site by a trigger strand, it follows the track by binding to and then cutting the DNA strands extending off of the staple strands on the molecular track," Stojanovic adds.

"Once it cleaves," Yan remarks, "the product will dissociate, and the leg will start searching for the next substrate." In this way, the spider is guided down the path laid out by the researchers. Finally, explains Yan, "the robot stops when it encounters a patch of DNA that it can bind to but that it cannot cut," which acts as a sort of flypaper.

Although other DNA walkers have been developed before, they've never ventured farther than about three steps. "This one," says Yan, "can walk up to about 100 nm. That's roughly 50 steps."

"In the current system," Stojanovic says, "interactions are restricted to the walker and the environment. Our next step is to add a second walker, so the walkers can communicate with each other directly and via the environment. The spiders will work together to accomplish a goal." Erik Winfree, associate professor of computer science, computation and neural systems, and bioengineering at the California Institute of Technology (Pasadena), adds, "The key is how to learn to program higher-level behaviors through lower-level interactions."

For more information, see the article "Spiders at the Nanoscale: Molecules that Behave Like Robots."