DNA-based nanotechnology has been around for more than 30 years, but it really took off in 2006, when DNA origami was featured on the cover of Nature. This form of origami, the folding of DNA into 2D and 3D shapes, was more of an art form back then, but scientists are now using the approach to construct nanoscale robots.

The basic principle of DNA origami is that a long, single-stranded DNA molecule will fold into a predefined shape through the base-pairing of short segments called staples. All that’s required is to ensure that each staple can find a complementary match to base-pair with at the right location elsewhere in the molecule. This approach can be used to create both 2D and 3D structures.

The idea behind the new work is that a DNA origami robot can be programmed to have a specific function based on a key, which can be a protein, a drug, or even another robot. Once the right key and the right robot find each other, the key drives a conformational (structural) change in the robot. The new shape causes the robot to perform a programmed function, such as releasing a drug.

More recently, scientists from Harvard and Bar-Ilan Universities have figured out how to use DNA origami to make robots that behave like fundamental logic units. The scientists used these DNA-based discrete elements to construct a collision-based computer, with the collisions being between a key and a robot. Various logic gates—AND, OR, XOR, NAND, NOT, CNOT, and a half adder—could be put together using different combinations of robots.

The DNA gates all take two inputs in the form of other molecules. AND gates require that both inputs be present to open, while OR gates only require that one be present. In the diagram below, the far left block diagram represents an AND gate, and the one next to it depicts an OR gate. Using the same principles, the DNA origami strands can be synthesized to form different logic elements, as shown by the XOR and half adder.

Using this technology, the scientists constructed a logically complete NAND gate and a NOT (or inverter) gate.

A solution containing these specially constructed DNA origami elements was then injected into cockroaches to demonstrate that these synthesized logic elements can work in a biological context. In the case of the cockroaches, the scientists extracted haemocytes (the invertebrate’s version of a white blood cell) and validated the effectiveness of the robots’ ability to respond to their programmed keys within the cells.

The scientists propose that their DNA origami system could serve as a controller for drug release throughout different disease states. Their design involves three effector robots that all carry a specific drug. These robots respond to four regulator proteins (“cues”) that act as inputs and trigger a layer of logic gates (AND and OR). The output is a specific combination of drugs tailored to the combination of proteins present.

Similar systems could also release chemicals that provide information on biochemical and physiological function; these chemicals can then be used as a diagnostic tool. The authors propose that this sort of system would allow the control of a high number of drug combinations.

Nature Nanotechnology, 2014. DOI: 10.1038/NNANO.2014.58 (About DOIs).