The experimental therapy, detailed August 13 in Science Translational Medicine, is inspired by a rare genetic mutation that gives a small number of people an extraordinary ability: resistance to nearly all viral infections.
Rare disorder reveals hidden defense
About 15 years ago, Columbia immunologist Dr. Dusan Bogunovic began studying patients with a rare immune condition known as ISG15 deficiency. Though these individuals were more prone to certain bacterial infections, they seemed to shrug off viral illnesses without ever developing symptoms.
Closer study revealed that the mutation caused a constant, low-level state of immune activation, a kind of background inflammation that was highly effective at blocking viruses. “The type of inflammation they had was antiviral,” Bogunovic recalled in a Columbia University statement.
Turning biology into therapy
Instead of reproducing the harmful aspects of ISG15 deficiency, Bogunovic’s team identified 10 specific proteins responsible for most of the antiviral protection. They then engineered an mRNA-based therapy, similar in design to COVID-19 vaccines, that prompts cells to briefly produce those proteins.Delivered through the nose into the lungs of mice and hamsters, the treatment significantly reduced replication of both influenza and SARS-CoV-2, the virus that causes COVID-19. In cell culture tests, the therapy appeared to resist a wide variety of viruses.
A temporary but powerful shield
Unlike a vaccine, which builds lasting immunity to a specific pathogen, this treatment provides only short-term protection, estimated at three to four days in animals. Researchers say that could make it particularly valuable at the beginning of outbreaks, giving first responders, health workers, and high-risk populations an immediate layer of defense while vaccines are still in development.The therapy also does not interfere with long-term immunity, meaning patients could still develop protective memory after infection or vaccination.
Challenges ahead
The concept remains in early stages. Researchers say improving the delivery system, ensuring enough of the proteins are produced in the right tissues, is the biggest hurdle before moving into human trials. More work is also needed to determine how long protection lasts and how safe repeated dosing might be.
Still, experts say the findings are promising. By activating the body’s own antiviral machinery, the therapy could offer a virus-agnostic defense that works even when the identity of a new pathogen is unknown.
