DNA Robots Can Deliver Molecular Packages

Conceptual illustration of a DNA robot sorting two types of cargo molecules.
Illustration: Ella Maru Studio
Conceptual illustration of a DNA robot sorting two types of cargo molecules.

Miniature robots with arms and legs made of DNA can sort and deliver molecular cargo, a new study finds. Such DNA robots could be used to shuffle nanoparticles around on circuits, assemble therapeutic compounds, separate molecular components in trash for recycling, or deliver medicines where they need to go in the body, researchers from the California Institute of Technology in Pasadena say.

“Just like electromechanical robots have been sent to places that are perhaps too far for humans to go to—for example, on another planet—if we truly master the ways of engineering molecular machines, we would be able to build molecular robots and send them to places that are perhaps too small for humans to go to—for example, inside the bloodstream,” says study senior author Lulu Qian, an assistant professor of bioengineering at Caltech.

The new robots are made from three basic modules that are each brief snippets of DNA. One module is a “leg” with two “feet” for walking; another is an “arm” with a “hand” for grabbing onto cargo; and the last can recognize specific delivery points and make the hand release its cargo at those spots.

The scientists had their robots walk on 58-by-58-nanometer pegboards made of DNA origami. Each pegboard consisted of a long strand of DNA held together in the shape of a sheet by short pieces of DNA that served as staples, says Anupama Thubagere, a bioengineer at the Caltech and the study’s lead author.

Each of the DNA robot’s feet could bind to the DNA of the pegboard. However, each robot was designed so that only one of its two feet could anchor onto the board at any one time, while the other floated freely, Qian explains.

When random molecular fluctuations caused this DNA robot’s free foot to encounter the pegboard, it latched on, freeing the other foot. In this manner, the robot could walk in a random direction across the pegboard. The length of the DNA robot’s leg and foot controlled the length of its step—in this case, 6 nanometers.

When this DNA robot encountered cargo molecules tethered onto the pegboard, it grabbed them with its hand and carried them until it detected a delivery point that could stick to the cargo. This cargo consisted of fluorescent molecules the scientists could easily track, which were tagged with DNA strands tailored to snag onto the robot’s hand.

In experiments, the researchers had DNA robots explore a pegboard and sort two different kinds of cargo—three fluorescent yellow molecules and three fluorescent pink molecules—that were randomly scattered on the surface of the DNA origami into two specific locations. The researchers note that individual robots could sort these molecules with an 80 percent success rate in 24 hours, and adding more robots shortened the delivery time.

One step for these new DNA robots took 5 minutes. On average, it took each robot about 300 steps to complete the cargo-sorting task, which is an order of magnitude more steps than previous DNA robots were capable of taking while performing tasks in addition to walking, Thubagere says.

Although this new molecular machine is not the first DNA robot, this work “is one of the first steps toward developing the building blocks for general-purpose DNA robots,” Qian says. “We showed how a seemingly complex task, cargo-sorting, and potentially many other tasks that DNA robots can be programmed to do, use very simple modular building blocks. This is also the first example showing multiple robots collectively performing the same task.”

The scientists note their DNA robots could get tailored to work with many different kinds of cargo, and that multiple robots could sort different materials in parallel. Future DNA robots could also possess multiple arms and hands to carry multiple molecules simultaneously.

Future research can add modules to these molecular robots to help them move faster, or to help them mark where they have been and to follow such tracks “similar to how ants find direct paths between nest and food,” Qian says. “That way, the robot would be able to transport cargo molecules more efficiently. We are also interested in adding simple communication between robots, so they can cooperatively perform more complex tasks, like a swarm.”

She hopes the work will inspire more researchers to develop modular, adaptive DNA robots for a diverse range of tasks, “to truly understand the engineering principles for building artificial molecular machines, and make them as easily programmable as macroscopic robots.”

The researchers detailed their findings in a paper in the September 15 issue of Science.

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