Authored by Olivia Qin
Art by Ashley Chopra
Paper-folding is a mesmerizing form of art capable of transforming plain sheets into mythical creatures and snowflake fractals. Yet, its value surpasses mere visual gratification. The fluidity and flexible nature of this ancient art is promising for medical practices where microscopic mobility is essential. Although origami is a new area of scientific study, researchers have confirmed its remarkable potential in advancing the capabilities and effectiveness of biomedical instruments, models, and techniques. In this interdisciplinary field where origami and medicine coalesce, modern science transforms a once purely aesthetic form of art into a promising direction for the future of medicine.
The most impactful attribute of origami in medicine thus far is its ability to transform freely at microscopic levels. In 2003, a British-Japanese team from Oxford University presented a stainless-steel stent prototype with an origami water-bomb base as the underlying groundwork. When fabricated using bioplastic, the stent was able to maneuver into an arterial blockage and expand its diameter from 12 mm to 23 mm . The flexible but sturdy nature of this design allows for efficient function with minimal risk. Currently, surgeons perform angioplasties using grafts of metal mesh and polyester. Though this method temporarily relieves artery blockages, frequent mesh fractures and graft ruptures pose serious threats of restenosis, where tissue in-growth through mesh openings block the open lumen . The origami stent prototype offers a pragmatic solution while also optimizing tensile strength with a shape memory alloy (SMA) foil that prevents collapse. This crucial step forward in biomedical research creates hope for more effective and long-lasting surgical treatments for chronic diseases, including coronary artery stenosis and aortic aneurysm.
In addition to coronary stents, scientists have also developed DNA origami nanostructures (DONs) for medical modeling and performance of specialized tasks in the bloodstream and tissues. Synthesizing these nanostructures involves graphing three-dimensional polyhedral meshwork to create single strand route scaffolds . Prior to this, strands of oligonucleotides, also known as staple strands, are assigned to sequence designs and arranged on the DNA backbones. Once materialized, the structures self-assemble into three-dimensional nanoparticles based on the arrangement of staple strands . This method of DNA modeling and nanoparticle construction is essential in biomedical research with its potential to synthesize encoded DNA nanostructures in living cells. Current in vivo therapies with Luxturna and Zolgensma injections are able to help treat inherited retinal disorder and spinal muscular atrophy, respectively, by stimulating the production of missing proteins . By applying origami nanoparticle modeling and DNA construction, there is a high likelihood of improving treatments by surpassing present limitations, such as the possibility of protein misfolding. Furthermore, investigating the practical applications of DNA origami may lead to the discovery of effective in vivo genetic therapies for inherited disorders, such as classical hemophilia, as well as acquired diseases including atherosclerotic arterial disease.
Using the same concept of DNA origami, synthetic nanoparticles can also function as microscopic transporters for drug encapsulation in cancer therapy. As the scientific community continues to evolve its understanding of cancer biology, the development of technologies that spare healthy tissues while delivering cytotoxic drugs to tumor cells have lagged behind . With the ability to manipulate the structure and responses of self-assembling nanoparticles, origami has become a promising approach to equipping drug nanocarriers with ligands and environmentally responsive molecular switches that target tumor cells and leave healthy ones unaffected. For instance, a cylindrical nanoparticle carrying thrombin, an enzyme that promotes blood clotting, can bind to a molecular trigger that appears in a specific tumor, prompting the release of thrombin. The local formation of blood clots occludes blood vessels that supply the tumor, leading to tumor necrosis . Since all solid-tumor-feeding vessels are similar in nature, the capacity of origami-based nanoparticles to seek out and react to tumor-specific triggers provides a hopeful gateway into effective therapy for currently untreatable cancers.
Furthermore, applying operative DNA particles to the construction of self-sustaining cells is promising in the context of more complex operations, especially organ transplants. Using the potential of DNA origami to culture functional cells, it is plausible for scientists to specialize these cells for different organs, such as the heart or kidneys . The intricacy and sheer number of required designs pose practical barriers. Regardless, this hypothesized method has taken a turn toward becoming a reality with the onset of four-dimensional bioprinting of tissue-engineered implants. Previously, emission tomography has confirmed effective absorption of radiolabeled DONs by kidneys to ameliorate acute kidney injury (AKI) in mice . The DONs self-arranged for exclusive absorption in the kidneys. If scientists tailor DONs to different cell types, it would be possible to not only stimulate and accelerate tissue growth in a damaged organ, but also grow entire transplantable organs modified for individual patients. Moreover, the required materials and equipment for working with DONs are relatively inexpensive in comparison to those for treatments that are available today. With this technology, the promising contributions of this cost-effective method are no longer science fiction.
Though seemingly incompatible before, the traditional art of paperfolding has merged into medicine, paving new paths for the improvement of surgical instruments, biomedical modeling, in vivo therapies, and organ transplants. Further research on precise molecular interactions and growth processes are necessary to apply these newly developed methods and technologies to practical situations. However, it is undeniable that this artistic and intellectual crossover is revolutionizing the field of medicine.
Islam, M. S., Kuribayashi-Shigetomi, K., Kabir, A. M. R., Inoue, D., Sada, K., & Kakugo, A. (2017). Role of confinement in the active self-organization of kinesin-driven microtubules. Sensors and Actuators B: Chemical, 247, 53-60.
Aksel, T., Yu, Z., Cheng, Y., & Douglas, S. M. (2020, October 19). Molecular goniometers for single-particle cryo-electron microscopy of DNA-binding proteins. Nature News. https://www.nature.com/articles/s41587-020-0716-8.
Ljubetič, A., Lapenta, F., Gradišar, H., Drobnak, I., Aupič, J., Strmšek, Ž., ... & Jerala, R. (2017). Design of coiled-coil protein-origami cages that self-assemble in vitro and in vivo. Nature biotechnology, 35(11), 1094-1101.
Jiang, D., Ge, Z., Im, H. J., England, C. G., Ni, D., Hou, J., ... & Cai, W. (2018). DNA origami nanostructures can exhibit preferential renal uptake and alleviate acute kidney injury. Nature biomedical engineering, 2(11), 865-877.
Linko, V., & Kostiainen, M. A. (2016). Automated design of DNA origami. Nature Biotechnology, 34(8), 826-827.