Influenza remains one of the most stubborn and unpleasant infections on the planet.
It returns every winter, mutating, evading the immune system, and eventually becoming drug-resistant. Now, scientists are proposing an unexpected approach that could literally deactivate the virus at the level of its genetic code .
It’s called SRISPR , and it’s a gene editing technology typically associated with the treatment of rare inherited diseases, as a tool. At the Pandemic Research Alliance Symposium in October, virologist Wei Zhao of the Peter Doherty Institute in Melbourne described a project his team is developing with colleagues.
The idea is to use Crispr not to edit human DNA, but to target the RNA of the influenza virus. This is important because the influenza genome is composed of RNA, which means the virus has a vulnerable spot that can be targeted. When discussing Crispr, the Cas9 enzyme, which acts on DNA , is usually mentioned most often. But in this story, Cas13 , a lesser-known relative of Cas9 , plays a key role. Cas13 is capable of cutting RNA.
In nature, none of these enzymes are produced by human cells. Instead, they are part of the arsenal of bacteria and archaea , where they play a role in their defense against viruses. Scientists want to temporarily transfer this principle to human cells and force them to briefly produce Cas13, which inactivates the influenza virus.
The proposed treatment format seems quite practical. It could be a nasal spray or an injection that delivers molecular instructions to the cells of the respiratory tract via lipid nanoparticles . The system consists of two parts. The first is the mRNA , which instructs the cell to produce Cas13 . The second is the guide RNA , a sort of address that tells Cas13 exactly which part of the viral RNA to cut. According to the team led by infectious disease specialist Sharon Lewin , after this intervention, the virus loses the ability to replicate normally and the infection is blocked at its most basic level.
The project’s authors envision the technology not only as a treatment for influenza already underway, but also as a potential preventative measure. For example, during particularly severe flu seasons, respiratory cells could be prepared for defense in advance, allowing them to respond more quickly to infection. Zhao’s comparison is simple and clear: it’s like keeping soldiers armed before they even encounter the enemy.
The main advantage of this approach is that Cas13 can target so-called conserved regions of the influenza genome. These are RNA fragments present in most strains and vital to the virus. Targeting these regions offers the possibility of creating a broad-spectrum drug effective against multiple influenza variants, rather than just a few specific ones. Compared to conventional antivirals, which lose effectiveness over time due to resistance, this versatility is particularly attractive.
Crispr-Cas13 isn’t the only candidate in the category of so-called pan-influenza drugs. Monoclonal antibodies, which specifically target resistant elements of the virus, are also under development, as are drugs that increase the production of interferons, the alarm molecules that trigger the immune attack. But influenza is so well adapted to survival that neither approach seems like an easy win.
The motivation to seek new solutions is understandable. Influenza A alone is estimated to kill between 12,000 and 52,000 people annually in the United States, and the figure varies greatly depending on the severity of the season. In this context, even a seemingly bold idea quickly becomes the subject of heated debate.
There is also skepticism, and it’s quite practical. Nicholas Heaton , professor of molecular genetics and microbiology at Duke University, highlights two risks. First, Cas13 is a foreign protein of bacterial origin, and the body could trigger an immune response against it . Second, there remains the risk of so-called off-target effects, when the tool targets not only viral RNA, but also the person’s own RNA.
Initial attempts to evaluate its safety have already been made. The Wyss Institute at Harvard University is using a “lung-on-a-chip” model, in which human lung tissue and vascular cells are assembled into a microsystem that mimics real-world processes. This is particularly useful for severe influenza, as during such infections the virus penetrates deep into the alveoli, the tiny air sacs where it actively replicates. According to Donald Ingber, one of the institute’s directors and an author of these models, experiments have shown that cells trained to work with Cas13 could suppress the replication of various strains, including H1N1 and H3N2. The team also observed no adverse off-target effects , and along with viral activity, inflammatory signals, which typically increase during infection, were also reduced.
Despite such encouraging results, a question remains, not so much about the concept itself as its implementation. Ingber emphasizes that targeting lipid nanoparticles with instructions to reach the deep lung alveoli is very difficult. And Heaton highlights another unfortunate characteristic of nature. Even if the attack targets critical regions of the genome, the virus can attempt to evade the pressure by mutating. As he puts it, “nature usually finds a way,” and these stories often end with the pathogen devising a workaround .
Interestingly, Heaton is also evaluating another strategy, also related to Crispr, but this time defensive. Instead of attacking the virus, they could alter the body’s environment to make it more difficult for the flu virus to enter cells and replicate. This version uses Cas9 , which helps identify human genes critical to the virus’s life cycle. Scientists are taking human cells, knocking out the genes one by one, and testing whether the flu virus retains its ability to infect and kill them. As a result, they have already identified an important target. Experiments show that the virus is highly dependent on the SLC35A1 gene, responsible for the presence of certain sugars on the cell surface. These sugars are what the flu virus uses as a receptor, or entry point.
It almost seems like a perfect “flu kill switch,” but it has its limitations.
Crispr-Cas13 promises to directly target the RNA of influenza viruses, cutting it and preventing them from replicating. This approach represents a breakthrough compared to traditional antiviral drugs because it acts at the genetic level, targeting the most critical regions of the virus . However, precisely identifying the sequences to target is complex, especially given the viruses’ extremely rapid ability to mutate.
Artificial intelligence and supercomputers are playing a key role in safely and effectively guiding Crispr. Advanced algorithms analyze millions of viral sequences from around the world and predict which regions are most conserved and vulnerable. This allows the AI to suggest optimal guide RNA sequences for Cas13, reducing the risk of unwanted effects on human cells.
In addition to designing the molecules , AI is used to simulate the interaction between Cas13 and cells, anticipating possible off-target effects . This allows scientists to optimize both the nanoparticles that carry the enzymes and the treatment dosage, reducing risks and accelerating the experimental phase.
Finally, artificial intelligence helps predict the evolution of the virus and potential mutations that could make it resistant . Thanks to these simulations, Crispr-Cas13 can be designed as an adaptive therapy, ready to target not only current variants but also future ones, paving the way for a new generation of “smart” antivirals.
Neither the CRISPR-Cas13 nasal spray nor the injections are yet ready for clinical use. But the very idea that influenza can be stopped not just through symptoms and the immune system, but by directly interfering with its RNA, seems like a step toward a new class of antiviral technologies. If scientists can solve the delivery and safety issues, the flu, which has kept humanity on tenterhooks for decades, could for the first time face an adversary capable of blocking it at the code level.
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