#  Could Recreating a Rare Mutation Grant Almost Universal Virus Immunity For Days?
robot (spnet, 1) → All  –  03:22:01 2025-08-25

"For a few dozen people in the world, the downside of living with a rare immune condition comes with a surprising superpower — the ability to fight off all viruses..." notes an announcement from Columbia University.

"At first, the condition only seemed to increase vulnerability to some bacterial infections. But as more patients were identified, its unexpected antiviral benefits became apparent."

Columbia immunologist Dusan Bogunovic discovered the individuals' antiviral powers about 15 years ago, soon after he identified the genetic mutation that causes the condition... Bogunovic, a professor of pediatric immunology at Columbia University's Vagelos College of Physicians and Surgeons, soon learned that everyone with the mutation, which causes a deficiency in an immune regulator called ISG15, has mild, but persistent systemic inflammation... "In the back of my mind, I kept thinking that if we could produce this type of light immune activation in other people, we could protect them from just about any virus," Bogunovic says.

Today, Bogunovic is closing in on a therapeutic strategy that could provide that broad-spectrum protection against viruses and become an important weapon in next pandemic. In his latest study, published August 13 in Science Translational Medicine, Bogunovic and his team report that an experimental therapy they've developed temporarily gives recipients (hamsters and mice, so far) the same antiviral superpower as people with ISG15 deficiency. When administered prophylactically into the animals' lungs via a nasal drip, the therapy prevented viral replication of influenza and SARS-CoV-2 viruses and lessened disease severity. In cell culture, "we have yet to find a virus that can break through the therapy's defenses," Bogunovic says...

Bogunovic's therapeutic turns on production of 10 proteins that are primarily responsible for the broad antiviral protection. The current design resembles COVID mRNA vaccines but with a twist: Ten mRNAs encoding the 10 proteins are packaged inside a lipid nanoparticle. Once the nanoparticles are absorbed by the recipient's cells, the cells generate the ten host proteins to produce the antiviral protection. "We only generate a small amount of these ten proteins, for a very short time, and that leads to much less inflammation than what we see in ISG15-deficient individuals," Bogunovic says. "But that inflammation is enough to prevent antiviral diseases...."

"We believe the technology will work even if we don't know the identity of the virus," Bogunovic says. Importantly, the antiviral protection provided by the technology will not prevent people from developing their own immunological memory to the virus for longer-term protection.

"Our findings reinforce the power of research driven by curiosity without preconceived notions," Bogunovic says in the announcement. "We were not looking for an antiviral when we began studying our rare patients, but the studies have inspired the potential development of a universal antiviral for everyone."

More coverage from ScienceAlert.

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