New research on mice examines the safety of DNA nanotechnology

New research on mice examines the safety of DNA nanotechnology

Advances in nanotechnology have made it possible to fabricate DNA structures for use in biomedical applications such as drug delivery or vaccine creation, but new research on mice is examining the safety of technology.

Using a technique called DNA Origami (DO) – a process that involves folding complementary DNA strands into double helices over and over again – scientists can construct a variety of small devices with complex shapes that can be injected into the body for to deliver medicines or perform other tasks. However, as this technology is still relatively new, researchers have been divided on whether nanostructures can cause dangerous immune responses or be toxic in other ways in animal systems.

Now a team of researchers from Ohio State University has taken a first step towards answering that question. The study, published in the journal Small, found that although high amounts of these DNA units can cause an easy immune response, it is not marked enough to be dangerous. Their results also suggest that different forms may be more favorable for different therapeutic applications.

DNA is incredible in terms of construction and how it can be manipulated and designed to form nanorobots in a very coordinated way. We believe that this technology, which has an incredible amount of potential, can be used to diagnose, treat and prevent diseases. “

Christopher Lucas, lead author of the study and researcher in mechanical and space technology at Ohio State

To test whether it can be done safely, Lucas’ team used mice to compare the biodistribution and toxicity of two distinct nanostructures: a flat single-layer 2D triangle called a “Tri” and a 3D rod-shaped structure named “Horse.” Over a period of 10 days, approximately 60 female mice received continuous IV injections of both DO structures. But to really test safety, the researchers repeatedly dosed the mice at a concentration 10 times higher than in previous studies.

Although researchers saw that Tri and Horse created form-dependent inflammatory responses, as the response decreased over time, they showed that the immune response was relatively harmless in the long run. “It was a modest immune response, but it was not toxic to the animals,” Lucas said. “Understanding that was really the key as we move towards preclinical development and prepare the technology for drug delivery applications.”

When the experiment ended, the team also collected and imaged all the mice’s major organs, blood and urine to track the final distribution of the device throughout the body. The results showed that both types of nanostructures were internalized by a variety of immune cells, but the amount of DO still left differed due to their initial concentrations and how long they permeated the body. Because they are biocompatible, nanostructures also happen to cleanse the body relatively quickly, Lucas said. And that’s a good thing, especially if researchers want to ensure that these devices can be used to target only sick cells.

But it is difficult to predict what challenges other types of nanostructures may encounter in a human or animal body.

“Once you put things into a biological system, there’s just so much variety to consider,” said study co-author Carlos Castro, a professor of mechanical and space technology.

As for what happens next, as they have shown that the technology is not toxic to mice, the team wants to start charging the devices with chemotherapy drugs and start learning how to use the devices to effectively target cancer cells in animals. “We’re just scratching the surface,” Castro said. “We unveil a whole new set of interesting issues that we can dig deeper into.”

This research was supported by the National Institutes of Health.

Source:

Journal reference:

Lucas, CR, et al. (2022) DNA Origami Nanostructures induce dose-dependent immunogenicity and are non-toxic up to high doses in vivo. Small. doi.org/10.1002/smll.202108063.

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