At a Glance
- Cas13 can cut influenza RNA, offering a new antiviral strategy.
- Researchers plan a nasal spray or injection using lipid nanoparticles.
- Influenza A kills up to 52,000 Americans each year.
- Why it matters: A new tool could prevent and treat flu without strain-specific drugs.
A brief intro paragraph: “At the October Pandemic Research Alliance Symposium, virologist Wei Zhao unveiled a bold plan to use the RNA-editing enzyme Cas13 as a next-generation flu therapy. The approach could turn the respiratory tract into a frontline defense by delivering Cas13 directly to infected cells.”
The Concept: Cas13 Against Flu
Cas13, unlike the more familiar Cas9, targets RNA rather than DNA. In human cells, the influenza genome is RNA, making it a perfect target. Zhao and colleagues aim to use lipid-nanoparticle-encapsulated mRNA to make Cas13 in the respiratory tract, guided by a short RNA sequence that directs the enzyme to a conserved region of the virus.
- Deliver mRNA encoding Cas13.
- Deliver guide RNA.
- Cas13 cuts viral RNA, halting replication.
Proof of Concept: Lung-on-a-Chip
Harvard’s Wyss Institute tested the strategy on a lung-on-a-chip model. The Cas13-expressing cells suppressed H1N1 and H3N2 strains with no detectable off-target effects, according to Donald Ingber.
Donald Ingber stated:
> “We didn’t see any off-target effects, which was amazing.”
> “We suppressed viral replication, but also the molecules that mediate inflammation which are secreted when your tissues are infected.”
The study also showed reduced inflammation markers, suggesting dual benefits.
Challenges and Next Steps
Delivering the nanoparticles deep into alveoli remains a technical hurdle, and the immune system may react to the bacterial enzyme. Nicholas Heaton warns about potential immune responses and off-target RNA cleavage.
Nicholas Heaton said:
> “I like the idea of it, but it’s [still] putting a foreign protein from a bacteria into someone’s body… So will the body make an immune response against it?”
> “Typically, what we find is that nature has a way… It’s like with the old Jurassic Park movie.”
Heaton is also exploring Cas9 to knock out the human gene SLC35A1, which flu uses as a sugar receptor. Reducing this gene’s activity could make cells less hospitable to the virus, but safety remains uncertain.
| Feature | Conventional antivirals | Cas13 approach |
|---|---|---|
| Target | Specific strains | Conserved viral RNA |
| Delivery | Oral/IV | Nasal spray or injection |
| Off-target risk | Low | Potential |
While the data are promising, the technology must still prove safety and efficacy in humans before it can become a public health tool.
Key Takeaways
- Cas13 can be engineered to cut influenza RNA in conserved regions.
- A lipid-nanoparticle delivery system could turn the respiratory tract into a frontline defense.
- Technical and immune-response challenges remain before clinical use.
If successful, the Cas13 nasal spray could add a powerful new weapon to the fight against seasonal and pandemic influenza.
