DNA Origami: How This Nanotechnology Could Advance Medicine

By Dr. Priyom Bose, Ph.D.Reviewed by Frances BriggsOct 3 2025

Similarly to the artistic technique of folding paper into ornate shapes,  DNA origami is a self-assembling technique of precisely folding single-stranded DNA scaffolds into well-defined nanostructures.¹ First proposed in 2006, in 2025 it is becoming a plausible approach in biomedicine. Here, we explore exactly what that looks like. 

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DNA is a macromolecule composed of adenine, thymine, cytosine, guanine, phosphoric acid, and deoxyribose. Technological advances have made DNA synthesis easier than ever before, making DNA nanotechnology a reality.

Usually, DNA nanostructures are designed through both top-down and bottom-up methods. The top-down method involves reducing the size of large, complex DNA structures to the nanoscale, while the bottom-up approach takes the smallest components, building them up like Lego into a large, complicated nanostructure. Despite being more fiddly, this bottom-up approach results in a more programmable, predictable DNA assembly.³

Rothemund first proposed the concept of DNA origami in 2006, based on this bottom-up self-assembly.⁴ This approach involved building large, randomly designed DNA nanostructures by folding a long DNA strand.

Over the years, this technology has evolved. It can now create a specific DNA pattern that resembles DNA origami boxes, highly complex two-dimensional (2D) and three-dimensional (3D) structures. Scientists have developed strategies to customize such structures using a geometry-triggered sequence design approach.

How are DNA origami shapes made?

Using hundreds of short DNA oligonucleotides, known as staple strands, a long, single-stranded DNA scaffold is created, which can then be folded into any desired pattern or shape with nanoscale precision. Staple DNA strands are designed to bind at specific sites on the scaffold via Watson-Crick base pairing. The scaffold DNA strand acts like the sheet of paper, and can be folded to create ornate architectures.⁵

Using this long DNA scaffold for folding avoids the need for hybridization. By hybridizing specific sites of the scaffold with staple strands before folding, the resulting structures are more precise, with improved DNA assembly.

The DNA origami technique reduces the risks of unwanted arrangement errors and cuts the time traditionally required for constructing DNA nanostructures. Being able to customize shapes precisely allows researchers to create versatile nanostructures capable of sensing, computing, and actuating. 

It also offers addressability with controlled stoichiometry and nanometric precision, making it an effective platform for displaying functional molecules (such as small molecules, proteins, and nanoparticles) in customizable nanoscale spatial patterns.

To date, researchers have employed several methods to functionalize DNA origami nanostructures. Direct chemical modification of staple strands with functional molecules to functionalize DNA origami nanostructures. This strategy has been widely used for protein patterning on DNA origami nanostructures.¹

DNA origami applications in medical research

DNA nanostructures possess an inherent biocompatibility, biostability, and high tissue penetration, properties that are hugely favorable in biomedical applications.⁶ 

Biosensing

Since 2008, when DNA origami was first used in biosensing, the field has accelerated. Many nanomaterial types, such as gold nanoparticles and quantum dots, have been used in the development of biosensors, which are widely employed in disease diagnosis and drug discovery. When the technique was first used, scientists created a 2D rectangular structure constructed with single-stranded overhang sequences at specific sites for RNA detection.

DNA origami's modularity allows for the integration of barcoded probes, enabling simultaneous detection of multiple RNA species. It has also been used to create nanochips to detect antibody-antigen interactions.

One interesting case by Sigl et al. involved the design of a programmable icosahedral shell system using the DNA origami method for virus trapping, which successfully captured hepatitis B and adeno-associated virus particles.⁷

Biocatalysis

Cellular metabolism is associated with a series of complex enzymatic reactions that convert substrates to various metabolites for cell growth and maintenance. These multiple enzyme complexes are well defined and support biochemical cascade reactions in living organisms.

Substrate channeling plays a critical role in several metabolic pathways, including fatty acid synthesis and the tricarboxylic acid cycle. To mimic substrate channelling for biocatalysts, researchers have developed multienzyme cascades that can be applied to diagnostics and synthetic biology.

DNA origami nanostructures can be used as carriers for fabricating these multienzyme cascade systems due to their excellent programmability and addressability. Recently, in a study in Nano Trends, DNA origami was used to assemble and enhance the activity of three-enzyme sequential cascades for therapeutic applications, particularly in cancer treatment.⁸

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Drug delivery

DNA origami is often used in drug delivery because designing structures in this way can lead to low cytotoxicity, superior biodegradability, and unique programmability and addressability.

Several compounds with therapeutic efficiency, such as nucleic acid molecules, small molecule drugs, and protein drugs, can be loaded onto the DNA origami nanocarriers via hybridization, intercalation, or covalent binding. For example, scientists have encapsulated doxorubicin into DNA origami nanostructures for anticancer treatment.⁹

DNA origami has also been used as a nanocarrier in the targeted delivery of the antimicrobial enzyme lysozyme. A recent study showed scientists have developed a smart DNA origami nanorobot to deliver thrombin to tumor-associated blood vessels.⁹

One of the primary challenges of DNA origami nanostructures is maintaining stability under physiological conditions, including low Mg²⁺ concentrations and specific serum concentrations. To address this, scientists are developing a computational tool to design DNA origami nanostructures with improved stability in biological conditions, but more research is needed.¹ 

Conclusions

Despite being first established almost two decades ago, the integration of DNA origami is still in progress in medical applications. Developing studies have revealed its efficacy and strength in biomedical applications, but comprehensive in vivo assessments are still needed before it can be applied to humans.

References

1. Li L. et al. DNA origami technology for biomedical applications: Challenges and opportunities. MedComm – Biomater Appl. 2023; 2(2), e37. https://doi.org/10.1002/mba2.37
2. Minchin S, Lodge J. Understanding biochemistry: structure and function of nucleic acids. Essays Biochem. 2019;63(4):433-456. doi: 10.1042/EBC20180038.
3. Zhan P. et al. Recent Advances in DNA Origami-Engineered Nanomaterials and Applications. Chem Rev. 2023; 123, 7, 3976–4050. https://doi.org/10.1021/acs.chemrev.3c00028
4. Yan X, et al. Bottom-Up Self-Assembly Based on DNA Nanotechnology. Nanomaterials (Basel). 2020;10(10):2047. doi: 10.3390/nano10102047.
5. Hong F, et al. DNA Origami: Scaffolds for Creating Higher Order Structures. Chem Rev. 2017;117(20):12584-12640. doi: 10.1021/acs.chemrev.6b00825.
6. He Z, et al. Self-assembly of DNA origami for nanofabrication, biosensing, drug delivery, and computational storage. iScience. 2023;26(5):106638. doi: 10.1016/j.isci.2023.106638.
7. Sigl C. et al. Programmable icosahedral shell system for virus trapping. Nat Mater. 2021;20(9):1281-1289. doi: 10.1038/s41563-021-01020-4.
8. Ahmed T. DNA origami-based nano-vaccines for cancer immunotherapy. Nano Trends. 2024; 8, 100060. https://doi.org/10.1016/j.nwnano.2024.100060
9. Ghosal S, et al. Unravelling the Drug Encapsulation Ability of Functional DNA Origami Nanostructures: Current Understanding and Future Prospects on Targeted Drug Delivery. Polymers (Basel). 2023;15(8):1850. doi: 10.3390/polym15081850.

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