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Handcrafted DNA nanorobot captures viruses for diagnostics and blocks entry into cells

A small four-fingered “hand” formed from a single piece of DNA can detect the virus that causes COVID-19 for highly sensitive rapid detection and can even block viral particles from entering cells to infect them, University of Illinois Urbana-Champaign researchers report. The nanorobotic hand, called NanoGripper, could also be programmed to interact with other viruses or to recognize cell surface markers for targeted drug delivery, such as for cancer treatment.

Led by Xing Wang, a U. of I. professor of bioengineering and chemistry, the researchers describe their progress in the journal Scientific robotics.

Inspired by the gripping power of the human hand and bird claws, the researchers designed the NanoGripper with four flexible fingers and a palm, all in a nanostructure folded from a single piece of DNA. Each finger has three joints, like a human finger, and the angle and degree of bending are determined by the design of the DNA structure.

“We wanted to create a nanoscale soft material robot with never-before-seen grasping functions, to interact with cells, viruses and other molecules for biomedical applications,” Wang said. “We are using DNA for its structural properties. It is strong, flexible and programmable.” However, even in the field of DNA origami, this is novel in terms of the design principle. We fold a long strand of DNA back and forth to make all the elements, both static and moving, into one. passed.”

The fingers contain regions called DNA aptamers that are specially programmed to bind to molecular targets (the spike protein of the virus that causes COVID-19, for this first application) and cause the fingers to bend to wrap around the target. On the opposite side, where the wrist would be, the NanoGripper can be attached to a surface or other larger complex for biomedical applications such as sensing or drug delivery.

To create a sensor to detect the COVID-19 virus, Wang’s team partnered with a group led by Illinois electrical and computer engineering professor Brian Cunningham, who specializes in biosensing. They combined the NanoGripper with a photonic crystal sensor platform to create a 30-minute rapid COVID-19 test that matches the sensitivity of standard qPCR molecular tests used by hospitals, which are more accurate than at-home tests but take much longer. time. .

“Our test is very quick and easy as we detect the intact virus directly,” Cunningham said. “When the virus is held in the hand of the NanoGripper, a fluorescent molecule is activated that releases light when illuminated by an LED or a laser. When a large number of fluorescent molecules are concentrated on a single virus, it becomes bright enough in our detection system to count each virus individually.”

In addition to diagnosis, the NanoGripper could have applications in preventive medicine by preventing viruses from entering and infecting cells, Wang said. The researchers found that when NanoGrippers were added to cell cultures that were then exposed to COVID-19, multiple grippers wrapped around the cell. exterior of viruses. This prevented the viral spike proteins from interacting with receptors on the surface of the cells, preventing infection.

“It would be very difficult to apply it after a person is infected, but there is a way to use it as a preventive therapeutic,” Wang said. “We could make an antiviral compound in a nasal spray. The nose is the hot spot for respiratory viruses, such as “COVID or influenza. A nasal spray with NanoGripper could prevent inhaled viruses from interacting with cells in the nose.”

The NanoGripper could easily be designed to target other viruses, such as influenza, HIV or hepatitis B, Wang said. In addition, Wang plans to use NaoGripper for targeted drug delivery. For example, fingers could be programmed to identify specific cancer markers and tweezers could deliver cancer treatments directly to target cells.

“This approach has greater potential than the few examples we demonstrated in this work,” Wang said. “There are some adjustments we would have to make with the 3D structure, stability, and targeted aptamers or nanobodies, but we have developed several techniques to make “This in the laboratory. Of course, it would require a lot of testing, but the potential applications for cancer treatment and the sensitivity achieved for diagnostic applications show the power of soft nanorobotics.”

The National Institutes of Health and the National Science Foundation supported this work. Wang and Cunningham are affiliated with the Carl R. Woese Institute for Genomic Biology and the U. of I. Holonyak Laboratory for Micro and Nanotechnology.

Editor’s Note: To contact Xing Wang, send an email @illinois.edu” title=”mailto:xingw@illinois.edu”>xingw@illinois.edu.

The article “Bio-Inspired Design DNA NanoGripper for Virus Detection and Potential Inhibition” is available at @aaas.org” title=”mailto:robopak@aaas.org”>robopak@aaas.org. DOI: 10.1126/scirobotic

This work was supported in part by NIH grants R21EB031310, R44DE030852, and R21AI166898.

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