DNA origami nano robots could one day carry out complex computer programs in the human body, helping to deliver cancer-killing toxins only to cancer cells while leaving the rest of the patient unharmed, according to .
How to Build a DNA Nanobot
By designing a DNA sequence just right, scientists can get the resulting floppy strand to stick to itself and bend into just about any shape they desire. The result is DNA origami, which creates 3D structures that are only nanometers in size. These creations hold their shape because the building blocks of DNA—adenine, thymine, cytosine, and guanine—cling only to specific partners.
These folded creations aren't just sculptures to look at: Researchers have found ways to make act as nano robots. For example, imagine a DNA nano robot shaped like a clamshell that is held closed by two shoestrings tied in a knot. Each shoestring is a strand of DNA known as an aptamer that can detect a specific target, like a protein linked with cancer. If both shoestrings detect their respective proteins, the knot unties, the clamshell opens, and voila—the robot delivers its payload, a cancer-killing antibody protein.
"The original application that motivated this work is cancer therapy," says researcher Daniel Levner, an expert in bioengineering at the Wyss Institute at Harvard University. "The problem with many current cancer therapy drugs is that they are not very targeted. Some kill any cell trying to divide, and since cancer cells divide more frequently, they are affected the most. But other cells divide too, like the ones in hair follicles, which is why hair falls out during chemotherapy. Scientists would like to develop therapies that recognize and kill only cancer cells."
Nanobots Working Together
These first DNA origami nano robots behaved much like computer science logic gates—specifically AND gates, which activated if and only if, say, both protein X and protein Y were present. But Levner and colleague Ido Bachelet of Bar-Ilan University in Israel realized "that while the AND function is great, it isn't able to reach the more complex decision making we were hoping for," Levner says. However, he says, they thought that if they created the DNA version of an exclusive-OR (XOR) gate, "you can essentially perform any computer program."
An XOR logic gate would activate if either protein X or protein Y was present, but not both. "We tried to make single nano robots more complex to behave like XOR gates, but that didn't turn out well," Levner says. "We then had the insight that instead of making a single complicated robot, we could take a group of different simple robot types that, when they interacted together, generated something more complex, an XOR gate."
To make this work, the researchers started with nanobots that behaved like AND gates. They then added two new kinds of nanobots—call them P1 and P2—designed to open the AND nanobot in response to protein X and Y, respectively. This allows the AND robot to open in response to protein X alone, protein Y alone, or both protein X and protein Y. This emulates an OR gate. Finally, they added another kind of nanobot, called N, which activates only if the proteins X and Y are present. When N bots activate, they close the AND gates. All these tiny DNA machines working in concert form an XOR gate.
The logic might be hard to decipher, but the importance is not: "We can get these nano robots to perform all kinds of complex tasks that simple drugs can't—we can potentially get them to carry out complex programs," Levner says. "For instance, if a cell has protein X and protein Y on its surface, but doesn't have protein Z, we know it's a particular kind of blood cell and not, for instance, a kind of cancer cell."
In their new study, the researchers successfully deployed their cocktails of DNA nano robots in living cockroaches and used those nanobots to release an antibody that recognizes the insect's hemocytes, which are analogous to human white blood cells.
"This is a huge step forward," says molecular technologist of Harvard University, who did not take part in this research. "This is the first time DNA-based computing was used in a living animal. This is also a great step forward to complex DNA-based computing systems."
To Church, this kind of bio-nano—nanotechnology based on biological materials—is better suited to biomedical applications than nanotechnology based on inorganic materials. "If you want to have a 'Fantastic Voyage' type of scenario where you have a small device that is moving around rather than just implanted, you want to be on the order of 5 microns or less," he says. "You also want low power consumption, and logic gates for biological systems can be five orders of magnitude less energy-consuming than an electronic circuit. And also, if you make your device out of the same materials the body is used to, you can have the advantage of compatibility with the body's immune system."
Still, there are problems standing in the way of using DNA nanobots in humans. One reason Bachelet's team did these tests with cockroaches is because their bodily fluids are low in nucleases, enzymes that break apart DNA. "Cockroaches make for a good system for the initial testing of DNA-origami-based technologies in living animals," Levner says. By contrast, the bodily fluids of mice, humans, and other mammals are much higher in nucleases, which helps fight infections, but poses a problem in using DNA robots in therapies.
However, a number of potential solutions exist to protect DNA robots in the human body. For instance, scientists might encapsulate the DNA robots in structures that protect them, attach chemicals that make the DNA more difficult to cleave, or even replace the DNA with molecules known as LNA that are similar to DNA but more resistant to attack, Levner says.
"There is more to be done before DNA nano robots could be used to treat human disease," Levner says. "However, seeing the nano robots perform a complex task within a living animal is a very important step in that direction, a result which we hope will motivate additional work towards this goal."
And as for your fears that DNA nanobots will become self-aware and malevolent, Levner says not to worry.
"A concern for some readers may be an association with the evil nano robots of sci-fi, which go on to take over the world," Levner says. "The DNA origami robots that we developed are not at all able to replicate themselves and could never pose the sci-fi threat. The DNA in our nano robots is a powerful building block, but otherwise it is no different than any other synthesized drug molecule."