Creating Useful Nanodevices by Manipulating DNA, a Versatile Material, at Will

Akinori Kuzuya
Department of Chemistry and Materials Engineering
Faculty of Chemistry, Materials and Bioengineering
Research Theme

Applying DNA Origami and Molecular Robots in Practice by Mastering the Art of Synthesis, Operation, and Handling of DNA

DNA is the universal means of genetic communication. Professor Akinori Kuzuya is attempting to utilize such DNA, with its well-known double-helix structure, made up of combinations of the four genetic letters (nucleotides) — A, T, G, and C — as a useful material/chemical compound, putting the concept of life aside. Professor Akinori Kuzuya freely programs DNA, even with unnatural artificial information, both chemically and biologically, by using his DNA synthesizing technique, in order to develop various DNA Origami devices or molecular robots. Artificial antibodies or artificial muscles are some of the feasible applications of these devices or robots in the medical field.

Any Sequence, with a New Letter. Producing DNA in Your Mind

DNA has transferred genetic information among the living beings on Earth for billions of years. DNA, a chemical compound called Deoxyribonucleic Acid, is a genetic storage medium based on the four nucleotides. It has extremely optimized properties for information storage and transfer. Complementary base-pairing — the rule that A pairs with T and G pairs with C — is one of such examples. Kuzuya and his team treat DNA as a simple and synthetic material — like plastic — and apply it to the development of various molecular devices.

“Recently, DNA has been developed for use as a molecular computer or even as a molecular memory that can store movie files within the sequence. Natural DNA is not very suitable for this purpose because its sequence is usually fixed. We, on the other hand, can join genetic letters one by one as we wish with the aid of our knowledge of organic chemistry. Even ‘artificial DNA’ with an unnatural letter ‘X’ is available to perform functions beyond nature.”

Another great advantage of the team is that they can produce large amounts of DNA at a reasonably low cost, says Kuzuya. “Typical amounts of DNA used in research labs are only in the microgram or nanogram range, which is almost an invisible miniscule amount. However, we can synthesize DNA in unusually large amounts as a visible and manageable material. Our investigation has been greatly accelerated thanks to the abundant supply of freely designable specimens.”

Applying “DNA Origami,” or “Nanoscale Weaving,” to Test Kits and Artificial Antibodies

Kuzuya is recognized as a key researcher of “DNA Origami.” This technique is used to prepare molecular nanostructures utilizing the self-assembly characteristic of DNA, maintained by complementary base-pairing between A, T, G, and C. Very long, single-stranded DNA binds to its counterpart as a carefully designed nucleotide sequence, according to the information expressed. It is then weaved into any desired structure such as nanosheets or 3D cubes, bottles, or even robots. Kuzuya applied this technique to prepare molecular pinching devices, dubbed “DNA Pliers.” They can find and clamp exactly one molecule between the jaws formed by the two lever portions, and shift to the closed form from the open X-shaped form. This structural change can be an indication, for example, of the existence of a cancer marker within the system.

“We are now working with a startup company to make daily health care test kits. We can freely tune and customize our devices according to the desired targets by applying all our knowledge and techniques in organic chemistry and biochemistry. We are all open to fulfilling any requests from the commercial or nonprofit sectors.” One ongoing project is to amplify DNA signals to a visible level, so they can be detected by the user just like in a pregnancy test. Professor Kuzuya further aims to create artificial antibody drugs from DNA Origami pinching devices.

DDS and Artificial Muscles.
Leaving Your Dreams to Autonomous DNA Robots

Members of the Intelligent Molecules Laboratory are also working on DNA hydrogels. DNA rapidly forms a special four-stranded structure in the presence of sodium ion. The team started to develop a new drug delivery system based on this property. “Body fluids contain a sufficient amount of sodium ion, so our new DNA material immediately turns into a gel upon injection. If you previously mix an anticancer drug into it, it is slowly released from the hydrogel, for a long-term effect. Animal tests have already shown promising results.”

Kuzuya is also engaged in “molecular robotics” and he created the world's first “molecular swarm robots” together with researchers from Hokkaido and Nagoya Universities. “Robots are composed of ‘sensors’ (that sense the surroundings), ‘processors’ (that process information), and ‘actuators’ (that respond to the input). We produced all the three with molecules.” The concept was inspired by flocks of birds. They form a flock even if there is no leader. Each bird is simply controlling the distance between itself and its neighbors, but the resulting flock acts as though it had intelligence. “We succeeded in commanding molecular robots to swarm and dissociate just by adding simple information to the system using DNA. We recently applied this system to establish molecular artificial muscles as well. The creation of molecular artificial neurons or artificial brains is not a fantasy anymore.”

An Encouraging Research Environment.
- Shaping the Future with “DNA + XXX”

Kuzuya first became interested in DNA while he was visiting labs to decide where he would conduct his undergraduate research. The way how one of his clubmates in the Japanese-archery club played with a DNA structure model looked quite fascinating to him, says Kuzuya. “I was completely enthralled with DNA when I began my own research project DNA indeed behaves just like I imagined and according to the sequence I designed but the targets are molecules now. It’s as though I am still playing with the structure models.” Kuzuya is confident that the research environment at Kansai University will be a great advantage for his own projects and joint projects on DNA robots and DNA Origami. “Most of the required, but costly, equipment is available for the department faculty and it is an ideal place for researchers. Our new idea can be reviewed at any time.”

Kuzuya feels that it is time to think about how to apply the “molecular puzzle” in the real world. With the aid of “reliable and versatile” material, Professor Kuzuya and the Intelligent Molecules Laboratory seek to create useful products for society based on their motto “DNA + XXX.”