Injection of DNA nano-device proven to be safe for medical use

ByLance T. Lee

Jul 16, 2022

Using DNA Origami, which involves folding complementary strands of DNA into double helices, scientists can create small devices with complex structures that could be injected into the body to deliver drugs or perform other tasks.

Mouse trials show nanodevices are not harmful at high doses

The ability to create DNA Structures for use in biomedical applications such as creating vaccines or drug delivery systems have been made possible by advances in nanotechnology, but a recent mouse study examines the safety of the technology.

Scientists can build a variety of tiny devices with complicated structures that could be implanted into the body to transport drugs or perform other tasks using a method called DNA Origami (DO), which involves bending complementary strands of DNA in double helices several times. However, due to the fact that this technology is still in its infancy, there is disagreement among experts as to whether the nanostructures could elicit dangerous immune responses or be toxic in other ways in animal systems.

Researchers at Ohio State University have now taken a first step towards providing an answer to this question. The research, which was recently published in the journal Small, found that while large amounts of these DNA devices can impact the immune system, they are not marked enough to be harmful. Their findings also imply that some medicinal applications might benefit more from different forms.

“DNA is amazing in terms of its construction and its ability to be manipulated and engineered to form nano-robots in a very coordinated way,” said Christopher Lucas, lead study author and mechanical and aerospace engineering researcher at the ‘Ohio State. . “We believe this technology, which has incredible potential, can be used to diagnose, treat and prevent disease.”

To test whether this 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 “Tri” and a 3D rod-like structure that received the nickname “Horse.” Over a period of 10 days, approximately 60 female mice received continuous IV injections of both DO structures. But to really test the safety, the researchers repeatedly dosed the mice at a concentration 10 times higher than in previous studies.

The researchers saw that Tri and Horse created shape-dependent inflammatory responses, but because the response waned over time, they showed that the immune reaction was relatively harmless in the long term. “It was a modest immune response, but it wasn’t toxic to the animals,” Lucas said. “Understanding this was really critical as we move into preclinical development and ready the technology for drug delivery applications.”

At the end of the experiment, the team also collected and imaged all major organs, blood and urine from the mice 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 remaining OD differed due to their original concentrations and the duration of their permeation in the body. Because they’re biocompatible, the nanostructures also cleanse the body fairly quickly, Lucas said. And that’s a good thing, especially if scientists want to make sure that these devices could be used to target diseased cells only.

But it is difficult to predict the challenges that other types of nanostructures might encounter inside a human or animal body.

“Once you put things into a biological system, there’s so much variability to take into account,” said study co-author Carlos Castro, a professor of mechanical and aerospace engineering.

As for what’s next, since they’ve shown the technology isn’t toxic to mice, the team wants to start loading the devices with chemotherapy drugs and start learning how to use the devices to effectively target cancer cells. with the animals. “We’re only scratching the surface,” Castro said. “We’re revealing a whole new set of interesting questions that we can dig deeper.”

Reference: “DNA origami nanostructures elicit dose-dependent immunogenicity and are nontoxic up to high doses in vivo” by Christopher R. Lucas, Patrick D. Halley, Amjad A. Chowdury, Bonnie K. Harrington, Larry Beaver, Rosa Lapalombella, Amy J Johnson, Erin K. Hertlein, Mitch A. Phelps, John C. Byrd and Carlos E. Castro, May 28, 2022, Little.
DOI: 10.1002/smll.202108063

The study was funded by the National Institutes of Health.


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