Origami is the English term for paper folding. The name comes from the Japanese word for the craft of paper folding (おりがみ), which combines the Japanese words for 'to fold' (ori) and 'paper' (kami). It is a method of folding paper to create structures with valleys and mountains, transforming it into desired three-dimensional shapes. It may be a technology that mimics nature. Looking at the buds of plants, one can see that the lines that eventually form the valleys and mountains of leaf surfaces are folded neatly.

Paper folding, which was once used for folding paper cranes to confess love, has transformed into a technology that saves lives. It folds the genetic material DNA into desired shapes to isolate only the cells affected by the hard-to-treat pancreatic cancer and to create cancer vaccines that enhance the body's immunity. By folding DNA into the shape of a virus that invades the body and injecting it, immune responses can be induced. Medical robots that travel through the body to heal wounds are also being developed using paper folding.

Professor Han Beom-soo (left) of the Department of Mechanical Engineering at the University of Illinois and postdoctoral researcher Dr. Choi Sae-rom successfully identified difficult pancreatic cancer tissues precisely using DNA origami based on the principles of paper folding. /Courtesy of the University of Illinois

◇Folding DNA strands into cylinders for drug delivery

The University of Illinois noted on the 22nd that "Professor Han Beom-soo and his research team from the Department of Mechanical Engineering successfully applied origami technology to DNA to distinguish pancreatic cancer tissues from normal tissues." The research paper, co-authored by Professor Choi Jong-hyun from Purdue University as a corresponding author, was published in the international journal 'Advanced Science' in February.

Pancreatic cancer is cancer that forms in the pancreas, which secretes digestive enzymes, and has a five-year survival rate of only 15.9%. The survival rate is so low because the pancreas is deep within the abdomen, making it difficult to detect with general screenings using endoscopies or ultrasounds. Early detection is challenging, and most patients are diagnosed at advanced stages.

Professor Han stated, "Using DNA origami allows for more accurate identification of pancreatic cancer tissues, aiding in surgical resection, as well as delivering drugs specifically to cancer cells." The research team has indeed proven this potential with human tissue modeled to mimic the pancreas.

The genetic material DNA consists of four bases: adenine (A), guanine (G), cytosine (C), and thymine (T). The order in which these bases are arranged determines the proteins that govern life phenomena. DNA is structured as a double helix, with two strands linked like a zipper, as adenine pairs with thymine and guanine pairs with cytosine.

If the order of the bases is designed well, one can create the desired three-dimensional nanostructures using the complementary pairing of these bases. DNA has such a stable structure that it can be extracted from fossils over a million years old, making it an optimal substance for encapsulating drugs and delivering them to the human body.

A shape made by inserting dye (purple) into the DNA strand and forming it into cylindrical and tile shapes. The amount absorbed in pancreatic cancer tissues was the highest at a specific size. /Courtesy of Advance Science

The research team created various sizes of cylindrical and tile-shaped structures by folding DNA. Dye was placed inside these structures and administered to cancer organoids. They then confirmed whether the shape or size of the DNA structures affected the absorbance rate in cancer tissues by examining the fluorescence produced by the dye.

Organoids are cultured structures resembling organs, derived from stem cells that can grow into all types of cells in the human body, and are referred to as mini-organs. The research team implemented human cancer tissues as organoids. Fluorescent imaging showed that cylindrical structures approximately 70 nm (nanometers; 1 nm is one-billionth of a meter) in length and 30 nm in diameter, and tile-shaped structures 6 nm in length and 30 nm in diameter, were absorbed the most by pancreatic cancer tissues. They were not absorbed by the surrounding normal tissues.

Professor Han commented, "When the sizes are similar, both the cylindrical and tile shapes show similar characteristics. This suggests that size may have a more significant impact than the shape of the DNA nanostructures. The fact that absorption characteristics decrease when the same cylindrical shape is either elongated or shortened supports this theory."

The research team is hopeful that DNA structures made via origami can also be used as drug delivery vehicles. The method involves encapsulating drugs within DNA structures and facilitating their absorption by cancer tissues. Professor Han noted, "This research is significant in that it demonstrates the selective delivery of anticancer agents or therapeutic genetic materials directly to cancer cells without side effects," and added, "We are currently preparing related follow-up studies."

Professor Han obtained his master's degree at Seoul National University and received his Ph.D. in 2001 from the University of Minnesota in the U.S. He moved to the University of Illinois in 2024 after serving as a professor at Purdue University. Co-corresponding author Professor Choi Jong-hyun obtained his master's degree at Yonsei University and received his Ph.D. in 2005 from the University of California, Berkeley.

A representation of DNA folded into the structure of the AIDS virus using the origami method. This can produce vaccine effects without causing any harm to the human body. /Courtesy of MIT

◇Developing cancer vaccines that boost immunity

DNA structures made through origami are also being developed as cancer vaccines. The principle of the vaccine is to inject non-toxic viruses or bacteria into the body to induce an immune response. It works like preparing for an attack after experiencing a small number of enemies beforehand, allowing for a swift response when actual enemies arrive. Cancer vaccines induce this immune response without directly destroying cancer cells like chemotherapy.

Ryu Joo-hee, a senior researcher at the Pharmaceutical Materials Research Center of the Korea Institute of Science and Technology (KIST), developed a cancer vaccine called 'DoriVac' using DNA origami technology in collaboration with the Dana-Farber Cancer Institute and Harvard Medical School in the United States last year.

The research team arranged CpG on the surface of the DNA nanostructures using origami technology. CpG refers to a sequence of cytosine (C) and guanine (G) bases that are consecutively linked and are particularly abundant in bacterial or viral DNA.

Cell experiments showed that the immune therapy effect was highest when CpG was arranged with a 3.5 nm interval. In tests on five mice induced with skin cancer, all but one survived for up to 150 days after being injected with DoriVac. In contrast, all mice that received no injection died by the 42nd day.

Vaccines also utilize structures made to resemble virus shells or shapes. Earlier, researchers at the Massachusetts Institute of Technology (MIT) successfully induced a powerful immune response in human immune cells by folding DNA into a structure resembling the Human Immunodeficiency Virus (HIV) using origami technology in 2020.

DNA origami was first developed by Dr. Paul Rothemund at California Institute of Technology (Caltech) in 2006. He created various NANO structures by consolidating DNA layers like folding paper. /Courtesy of Nature

DNA origami was first developed by Dr. Paul Rothemund at the California Institute of Technology (Caltech) in 2006. He published various nanostructures created by stacking DNA like paper in the journal Nature.

This technology has been recognized as a transformative technology from the beginning. The following year, the U.S. economic magazine Forbes selected and announced the top five most notable research achievements in nanotechnology from 2006, one of which was Caltech's DNA origami.

Now, 20 years later, the day when DNA origami will actually be used for patient treatments is approaching. The achievements of Korean scientists are particularly notable. Professor Kim Do-nyun and his research team from the Department of Mechanical Engineering at Seoul National University published a cover paper in Nature in 2023 on how to modify or move nanostructures using DNA origami.

Professor Kim has created a wireframe, akin to gold, for folding paper using DNA strands. By inserting such strands into DNA structures, complex structures can be formed and modified into desired shapes depending on the situation. Professor Kim expects that this DNA origami technology can be utilized for nanorobots aimed at drug delivery.

Professor Kim Do-nyun and his research team at Seoul National University developed a technology to modify NANO-sized DNA like paper folding, and published it as a cover paper in the international journal Nature. /Courtesy of Nature

References

Advanced Science (2025), DOI: https://doi.org/10.1002/advs.202410278

Nature Nanotechnology (2024), DOI: https://doi.org/10.1038/s41565-024-01615-3

Nature (2023), DOI: https://doi.org/10.1038/s41586-023-06181-7

Nature Nanotechnology (2020), DOI: https://doi.org/10.1038/s41565-020-0719-0

Nature (2006), DOI: https://doi.org/10.1038/nature04586