Engineered nanobodies improved respiratory defenses in preclinical study

• There are no current therapies designed to improve protection against multiple different respiratory viruses
• Engineered nanobodies improved protection against multiple viruses by bolstering respiratory mucus
• The bispecific design of the nanobodies works against viruses, like influenza, which can normally evade mucosal defenses

HOUSTON, JANUARY 21, 2026 ― In a multi-institutional study published today in Nature Nanotechnology, researchers from The University of Texas MD Anderson Cancer Center reported that engineered bispecific nanobodies successfully strengthened mucosal defenses in the respiratory tract, improving protection against influenza infection and reducing SARS-CoV-2 transmission in vivo.

Wen Jiang, M.D., Ph.D., associate professor of Radiation Oncology, has been researching different nanotechnologies for their potential use in delivering cancer therapies. That research has led to work with Liming Zhou, M.D., a postdoctoral student, and the late Charles Chan, Ph.D., assistant professor of surgery at Stanford Medicine.

“Most approaches to these types of viruses are limited to either one type of virus or relieving symptoms once someone is already infected,” Jiang said. “This study lays the groundwork for a promising new strategy to reinforce the body’s first-line mucosal defense against several types of respiratory viruses.”

What led to this study of nanobodies in respiratory mucus?

One reason that respiratory viruses, like influenza, can spread quickly is limited protection at the initial site of infection, the respiratory mucosa. Airway mucus is a first line of defense that can bind viruses and help prevent them from penetrating deeper into the respiratory tract. Influenza, however, can use an enzyme called neuraminidase to reduce mucus binding and facilitate infection.

One existing therapy for increasing the body’s ability to fight respiratory infections like these is oseltamivir (Tamiflu). It blocks the flu’s enzyme, trapping the virus and limiting its spread. However, this approach is not effective against other respiratory viruses that use different mechanisms to bypass the mucosal barrier.

In this study, scientists used an engineered nanobody, which is a very small type of antibody, to bind viruses to the mucus and prevent them from spreading infection.

One on end, the nanobody binds to viral proteins and, on the other, it binds to different proteins in the mucosal layer, allowing the mucus to trap viruses that would normally be able to break through. This method was effective at both improving protection and reducing transmission of multiple respiratory viruses, including influenza and SARS-CoV-2 in vivo.

What is the significance of this finding?

This novel approach has several distinct advantages over current strategies. Among the most significant is that it was effective in preclinical models of multiple respiratory viruses, rather than in targeting one specific virus, like current therapies.

The nanobodies also showed extended retention time in the respiratory system, which could reduce the frequency of delivery compared to other approaches. Additionally, the nanobodies were effective when given before exposure or after infection.

Unlike vaccines, which can take several weeks to generate a respiratory response, the nanobodies begin working immediately upon delivery, which could provide immediate, localized protection at the site of viral entry.

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Unfortunately, Chan passed away in 2024, prior to completion of the study. Jiang agreed to co-supervise the project to ensure its publication.

“Dr. Chan’s impact was extraordinary, particularly in stem cell biology, and his work will continue to shape the field for years to come. It was an honor to collaborate with his lab on this study,” Jiang said.

This research was supported by the National Institutes of Health, the Heritage Medical Foundation, the Wu Tsai Human Performance Alliance, the Stanford COVID Relief Funds, the California Institute for Regenerative Medicine, and the American Heart Association. A complete list of collaborating authors and their disclosures can be found with the full paper in Nature Nanotechnology.