Illinois bioengineering professor Xing Wang and his team have developed programmable DNA nanoplatforms that dramatically boost the effectiveness of antiviral molecules by arranging them in virus-mimicking patterns. By “blueprinting” DNA into virus-sized frameworks, the bioengineered structures enable multivalent binding that allows antiviral nanobodies and aptamers to latch onto viruses at multiple points simultaneously. This approach increased antiviral potency by more than 100-fold against pathogens such as SARS-CoV-2, HIV, and influenza, highlighting its promise as a broadly adaptable antiviral strategy. The work showcases how bioengineering at Illinois is leveraging DNA nanotechnology to create next-generation therapeutics for emerging and evolving viral threats.
Written by Ben Libman
The Wang Lab.
“We showed that you can “blueprint” DNA into virus-sized frameworks and then decorate them with antiviral nanobodies or aptamers arranged in exactly the right pattern to lock onto target viruses, turning existing weaker antiviral molecules into much more powerful and broad-acting inhibitors.”
For centuries, viruses have been one of mankind’s most lethal enemies. From smallpox to COVID-19, these tiny protein capsules have been responsible for hundreds of millions of deaths. Vaccines, though crucial, are not always enough; vaccines need time to be maximally effective, and don’t work equally well in everyone.
Antiviral medication can help fill the gaps, but often fall short. Traditionally, antivirals have been in the form of single, free-floating molecules that bind to one viral protein at a time. This method can be inefficient and limits an antiviral’s effectiveness. That is why bioengineering professor Xing Wang’s laboratory set out to create new platforms that could enhance the potency of antiviral molecules. Their solution was outlined in two recently published papers. One, in Advanced Science, was led by Saurabh Umrao, Abhisek Dwivedy and Dhanush Gandavadi. The other, in Nano Letters, was led by Tingjie Song, Jazmin Galván Achi, Varada Anirudhan and Dhanush Gandavadi. Both constituted an ingenious mirroring of the method viruses use to break into our cells.
When viruses attempt to penetrate a human cell, they don’t bounce around our body at random- they increase their odds by engaging in multivalent binding, or many simultaneous contacts that collectively create a stronger interaction. Wang’s lab was able to create a structure made of DNA that empowers antivirals to do the same, holding the molecules in a pattern that mirrors the virus and allows the antivirals to attack as a group.
“Spike proteins on the viral outer surfaces are organized with certain spacing and spatial patterns,” explained professor Wang. “When the respective nanobodies are organized on our DNA nanoplatforms to mirror the spacing and pattern of the corresponding spike proteins, the nanobodies can interact with the virus at many points at once instead of just one. This multivalent ‘lock-and-key pattern’ makes it much harder for the virus to detach or infect cells.”
Schematic illustration of a versatile two-dimensional nanoarchitecture with spatially patterned Nbs for protecting human host cells from viral pathogen infections. Image courtesy of Xing Wang.
The key to this platform is its DNA scaffolding. Professor Wang outlines why DNA is the right choice: “DNA is an exceptionally powerful antiviral building material because it’s like molecular Lego with a built-in instruction manual, and its base-pairing rules let us program DNA strands to self-assemble into precise 2D or 3D shapes with nanometer accuracy. That means we can position antiviral molecules with the right distances and angles to match a virus’s surface and easily redesign or scale those patterns just by changing the DNA sequence. Unlike many inorganic nanoparticles, DNA is biocompatible and, in our hands, non-toxic to cells.”
When antiviral nanobodies are organized in this way, the increase in effectiveness can be massive. Against SARS-CoV-2 this platform was up to 171 times stronger than antivirals alone. Against HIV, that number was as high as 233. When fighting influenza, these DNA nanostructures blocked over 95% of viral infections and boosted cell survival by up to 45%.
This technology can also be used in other contexts. These molecular platforms have the potential to be rapidly tailored to new variants or new viruses as they arrive, as Wang explains: “This is a platform technology rather than a one-off antiviral. By keeping the DNA framework and swapping the antiviral binders, the same design rules could, in principle, be extended from SARS-CoV-2 or influenza to other fast-evolving respiratory viruses.”
This project is a direct result of the Department of Bioengineering’s commitment to interdisciplinary collaboration. “None of this would be possible without close collaboration across DNA nanotechnology, virology, structural biology, and Vet Medicine at Illinois (Dr. Ying Fang at Urbana-Champaign, Dr. Lijun Rong at Chicago),” said Wang. “These partners bring a level of interdisciplinarity that we think will be essential for turning these kinds of programmable materials into real-world therapies.”
This technology still has a few steps before it’s ready for clinical use. Wang’s lab is preparing to test this platform on animal models and new viruses. From there, clinical partners will help bring this technology to clinical application. But the promise of this new antiviral platform is extremely exciting. Our battle against viruses is ongoing, but Wang may have designed one more weapon to help us fight back. It’s another way Bioengineering at Illinois is engineering the future of health.