Introduction

In this project, I explored a new way to fight influenza A by attaching an antiviral peptide called Urumin to a custom-shaped DNA nanostructure. By organizing the peptide on a DNA scaffold, we aimed to make it more potent, safer, and effective against multiple flu strains. This work was completed at the University of Illinois at Urbana-Champaign in collaboration with colleagues from Bioengineering, Animal Sciences, Pathobiology, Chemistry, and colleagues at Peking University and Chang’an University. 

Objectives

• Improve the antiviral potency of Urumin while using much lower doses

• Expand its activity across different influenza A subtypes (H1N1 and H3N2) and host-adapted strains

• Understand how Urumin interacts with the viral hemagglutinin (HA) protein at the molecular level

• Build and validate a stable DNA nanostructure to present Urumin in precise, multivalent patterns

• Test whether this approach can reduce disease in infected animals without harming normal immune responses

Results

We found that when Urumin was displayed on the DNA nanoscaffold, it blocked influenza A infection at nanomolar concentrations, about a 1,000-fold improvement over free Urumin, while keeping cells much healthier in culture. The platform worked against both H1N1 and H3N2 strains and reduced weight loss and mortality in infected mice, all while preserving virus-specific antibody and T-cell responses. These results suggest that DNA-based nanomaterials can greatly enhance existing antiviral peptides and could be adapted in the future to target a wide range of viral diseases.

Introduction

This project explores a new kind of antiviral platform that uses a honeycomb-shaped DNA nanostructure to display flu-binding nanobodies and aptamers in precise patterns that match the surface of the influenza A virus. By “pattern-matching” the virus at the nanoscale, the platform greatly strengthens how tightly these ligands bind and how effectively they block infection.

Objectives

• Design a stable, programmable DNA scaffold to present antiviral ligands in trimeric clusters.

• Compare free vs. scaffolded nanobodies/aptamers and measure changes in binding strength and antiviral activity.

• Test whether this geometry-matched approach works across multiple influenza A subtypes and host species.

Results

The scaffolded ligands showed up to ~1,000-fold stronger apparent binding to influenza viruses and achieved ~95–99% inhibition of infection in cell models, with significantly improved cell survival compared with free ligands. The platform performed well against several influenza A strains and in both murine and swine systems, suggesting a broadly applicable, modular strategy for future antiviral designs.

Introduction

In this project, I helped develop a rapid, low-cost lateral flow test (similar to a pregnancy strip) to detect Porcine Epidemic Diarrhea Virus directly on farms using pig oral fluid. The device uses a custom “DNA-Net” nanostructure that displays multiple PEDV-specific aptamers in a precise pattern, allowing the test to grab the virus’s nucleocapsid protein with very high affinity.

Objectives

• Create a simple, 10-minute test that farmers and veterinarians can use on-site.

• Achieve near–PCR-level sensitivity without RNA extraction or specialized equipment.

• Ensure high specificity so PEDV can be distinguished from other swine viruses.

Results

• Detects PEDV N protein down to ~1.33 ng/mL and ~278 viral copies per test in oral fluid.

• Reached ~95.8% overall accuracy in field samples (high sensitivity and specificity).

• No cross-reactivity with other common swine viruses and fully compatible with on-farm workflows.

This work was carried out at the University of Illinois at Urbana–Champaign in collaboration with veterinary and diagnostic partners, with partial support from the National Pork Board (NPB PR-006214). The same DNA-Net platform can be adapted to other animal and zoonotic pathogens, supporting broader One Health surveillance.