CRISPR Tools Offer a New Weapon Against Respiratory Viral Infections

Respiratory viral infections represent a major challenge to global health, with hundreds of thousands of deaths each year caused by viruses such as influenza, respiratory syncytial virus, or SARS-CoV-2. While vaccines and antiviral drugs play a key role, their effectiveness can be limited by the rapid evolution of viruses and the emergence of resistance. An innovative approach, based on CRISPR technology, enables direct targeting of the viruses’ genetic material or the cellular factors necessary for their replication.

This method uses programmable enzymes, such as Cas13 for RNA viruses or Cas9 and Cas12 for DNA viruses, capable of cutting specific viral sequences. Laboratory studies, on human lung cell cultures and in animal models, have shown that these tools can reduce the viral load of influenza or SARS-CoV-2. For example, the injection of Cas13a in the form of messenger RNA into the lungs of mice or hamsters has significantly reduced the amount of virus after nasal or aerosol administration.

One of the major advantages of this technology lies in its ability to adapt quickly. By targeting conserved regions of the viral genome—areas less prone to mutations—researchers limit the risk of viral escape. Additionally, the simultaneous use of multiple RNA guides allows targeting several parts of the genome, making it more difficult for resistance to emerge. This strategy, called multiplexing, has already proven effective against various variants of SARS-CoV-2 and could be extended to other respiratory viruses.

However, delivering CRISPR tools directly into the lungs poses challenges. Viral vectors, such as adenoviruses, allow prolonged expression of the enzymes but can trigger immune reactions or have size limitations for transporting genetic material. Lipid nanoparticles, on the other hand, offer a more flexible solution. They enable temporary expression, suitable for acute infections, and can be administered via aerosol. Recent studies have demonstrated their ability to efficiently deliver messenger RNA encoding Cas13 to the lungs of mice, with good tolerance and a marked reduction in viral load.

Another asset of CRISPR is its ability to modulate cellular factors involved in viral infection. For example, by blocking the expression of cathepsin L, an enzyme necessary for SARS-CoV-2 entry into cells, it is possible to reduce infection without directly targeting the virus. This approach has the advantage of limiting resistance risks, as it targets conserved cellular mechanisms rather than changing viral sequences.

The remaining challenges include optimizing delivery to prevent nanoparticles from being trapped by mucus or lung defenses, as well as minimizing side effects, such as immune reactions against CRISPR enzymes or delivery vectors. Health regulators also require robust data on the distribution of therapies in the body, their persistence, and their long-term safety before any clinical application.

In the future, integrating CRISPR technology with rapid sequencing methods could enable the development of real-time personalized therapies. By analyzing the genome of the virus present in a patient, it would be possible to design custom RNA guides to precisely target the infectious strain. Additionally, libraries of pre-designed guides could be stored and rapidly deployed in the event of an outbreak, providing an immediate response against emerging new viruses.

Finally, CRISPR could be combined with other approaches, such as antimicrobial peptides or antibodies, to enhance treatment efficacy. This combination could not only treat the viral infection but also reduce the use of antibiotics, thereby limiting the emergence of bacterial resistance. With continuous progress in delivery, safety, and regulation, CRISPR-based therapies could soon become an essential weapon in the fight against respiratory infections.

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DOI: https://doi.org/10.1007/s44370-026-00045-0

Title: CRISPR-based therapeutics to combat respiratory viral infections

Journal: Discover Viruses

Publisher: Springer Science and Business Media LLC

Authors: Piyush Baindara; Roy Dinata