DNA origami puts a smile on researchers’ faces

DNA and origami: there are two words you never thought you would see together. But they have indeed come together and they promise to revolutionise nanotechnology, the science of things that are really, really small.

"DNA origami is a technique for folding DNA into precise shapes on the nanoscale, ie objects about 1/10,000th of a human hair," says Dr Cathal Kearney, from the tissue engineering research group at the Royal College of Surgeons in Ireland.

“Unlike in natural biology, where DNA is used as an informational material to encode genes, in DNA origami the DNA is used as a structural material to build shapes.”

DNA, short for deoxyribonucleic acid, is the material inside our cells that stores all the information needed to keep them working. It is made of two long strands that are twisted together to form a double helix.

But surely origami is all about folding. So how does DNA get folded?

The DNA strands are like strings of pearls, threaded one after another on to twine. There are four different types of pearls in DNA, usually called A, T, C and G (short for adenine, thymine, cytosine and guanine).

The “pearls” on one strand can interact with the ones of the opposite strand, binding them together to form the double helix. But there are rules for this interaction: A can bind only to T, and C can bind only to G.

These specific binding rules are what makes DNA suitable for folding. If you construct strands with the right "pearl" sequence, you can make them interact with each other to form two- and even three-dimensional shapes. You can always control how they will bind by tweaking their sequence.

Building tiny structures

In 1982 researcher Nadrian Seeman proposed for the first time that DNA could be used as a material to build tiny structures. He said he got the idea from Depth, a print by artist MC Escher. The image depicts fish forming a large 3D structure by interacting with each other in a certain orientation. It apparently came into his head while having a beer in a bar in Albany and it inspired his DNA work.

It took him years to figure out the right way to build the structures, but he eventually managed to produce squares and triangles. In 1991 he fabricated the first DNA cube.

His method was lengthy and difficult, but in 2006 a novel, much easier method was introduced by researcher Paul Rothemund. It was he who originated the term “DNA origami”.

The method involved folding a large DNA sequence obtained from a virus by adding smaller, “sticky” sequences that acted as glue, guiding and holding the large strand in shape. The sequences of the “sticky” strands were determined by computer software.

The method proved so much easier that it allowed DNA to be folded not only in squares and triangles but also in star shapes and smiley faces. Production was also much faster: a matter of a few hours.

Rothemund’s images of folded DNA shapes were so striking that they were exhibited at the Museum of Modern Art in New York.

Since then, scientists have found ways of building even more sophisticated structures with a view to testing them for biological, chemical, medical and electronic applications.

Precious cargo

"These shapes can be used to deliver drugs and information to cells, as biosensors to test biological substances or for biocomputing," Kearney says.

For example, researchers were able to build a cubical box with a lid. The box can carry different cargoes, such as drugs for the treatment of disease.

Researchers were also able to equip the lid of the box with a “lock”, a compound that can be twisted or broken to open the lid when it binds to a specific molecule in the cell, which acts as a “key”.

By picking “locks” that can be opened only by compounds present in diseased cells, scientists are then able to specifically target the cargo in the box to the right place.

Delivering drugs is just one of the proposed applications for DNA origami. Because the technique allows the design and production of precisely shaped structures at incredibly small scales, they can also be used to develop tiny components such as electronic chips.

This stems from the fact that it is possible to stick various materials such as metal particles on to the DNA shape, also fostering applications in sensing and optical devices.

DNA ORIGAMI: THE FIGHT AGAINST CANCER
Dr Cathal Kearney's group at Royal College of Surgeons in Ireland is interested in applying DNA origami structures to the fight against cancer.

“We are collaborating with Prof Carlos Castro’s research group at Ohio State University, who are experts in fabricating DNA origami designs,” he said. “Our goal is to develop techniques and carrier materials to deliver DNA origami in the body for applications in cancer and tissue regeneration.”

Cancer is an attractive target for therapies based on DNA origami. Many conventional chemotherapy drugs target the cancer cell DNA by inserting themselves in the structure and affecting its ability to transfer information.

Because of this property, these drugs can easily be loaded into a DNA origami shape, as they simply insert within the structure.

Many cancer cells have developed ways to avoid being killed by chemotherapy drugs. It is said that these cancer cells have become resistant to chemotherapy. One of the main mechanisms these cells use is to pump the chemotherapy drugs out of the cell through specialised channels. They can do this because the drugs are very small compounds that can be easily expelled.

However, when the drug is inserted in a DNA origami shape, pumping out through this mechanism is not possible, and chemotherapy-resistant cancer cells are therefore killed. This approach has been successfully tested in the laboratory for breast cancer and leukaemia cells.

DNA origami vehicles could improve currently used chemotherapy and restore its ability to kill cancer cells. This would add value to existing drugs and positively impact cancer patients’ lives.