About This Project

Six years after COVID-19, the threat from emerging and re-emerging viruses remains. We need antiviral strategies that viruses cannot easily escape.

Therapeutic interfering particles (TIPs) are engineered virus variants that disrupt virus growth while triggering protective immunity. We hypothesize that next-generation TIPs can suppress viral replication in ways that are more resistant to viral escape than existing antiviral strategies. Our project will start work to test this hypothesis.

Ask the Scientists

What is the context of this research?

The COVID-19 pandemic reminded us how vulnerable society remains to rapidly evolving viruses. Vaccines and antiviral drugs can be highly effective, but viruses often evolve ways to escape them. Even today, SARS-CoV-2, influenza, measles, hanta and other viruses continue to circulate and re-emerge. While COVID is now managed more like other seasonal respiratory infections, we still lack durable strategies that remain effective as viruses evolve.

My lab studies how viruses grow, spread, and change over time. One lesson from our decades of research is that viral evolution is not an exception—it is the rule. This project explores a different approach to antiviral defense: harnessing naturally occurring defective viral genomes that arise during virus replication. These defective copies cannot cause disease but can interfere with normal virus growth. Understanding how they work may reveal new ways to control infections that remain effective even as viruses evolve.

What is the significance of this project?

The risk of future pandemics is increasing. Climate change, urbanization, and global travel are bringing humans into closer contact with birds, bats, wild rodents and other animals that harbor many viruses capable of infecting people. These shifting ecological boundaries increase the chances that new viruses—or familiar ones returning in new forms—will emerge and spread rapidly through human populations.

To prepare for this future, we need antiviral strategies that remain effective even as viruses evolve. Therapeutic interfering particles (TIPs) represent a promising possibility. TIPs are virus-derived genomes that replicate only in the presence of the virus and interfere with its growth. Because they depend on the virus to replicate, TIPs may evolve alongside it, potentially limiting the virus’s ability to escape. If successful, this strategy could provide a new class of antivirals designed to remain effective over longer time scales.

What are the goals of the project?

This project will begin testing whether therapeutic interfering particles (TIPs) can be engineered as durable antiviral agents. Our approach combines laboratory experiments with computational modeling to understand how viruses and TIPs grow and evolve together.

In the lab, we will test approximately 5 engineered TIP designs against 2–3 representative viral strains in cultured mammalian cells, with three independent biological replicates for each condition. We will measure virus growth, TIP abundance, and genetic changes using molecular assays and next-generation sequencing. In parallel, we will extend our computational models, simulating virus–TIP interactions to identify TIP designs that maximize interference while limiting viral escape.

These studies will generate the first quantitative data needed to evaluate whether TIPs can reliably suppress viral growth and resist evolutionary escape. The results will guide the development of next-generation antiviral therapeutics.