Scientists at Queen Mary University of London have developed a method to bypass cellular defenses against self-amplifying mRNA vaccines, allowing them to produce significantly more target proteins.
The breakthrough targets a fundamental flaw in self-amplifying mRNA (saRNA) technology. While standard mRNA vaccines provide instructions for cells to create a protein that triggers an immune response, saRNA is designed to replicate within the host cell. This replication should theoretically allow for longer-lasting protection at lower doses, speeding up global rollout and reducing costs.
However, the replication process creates double-stranded RNA (dsRNA), which the body recognizes as a viral threat. This triggers the cell’s natural anti-virus defenses, making the saRNA unstable and less capable of instructing the cell to produce the necessary proteins. Effectively, the cell’s own security system shuts down the vaccine before it can do its job.
The Role of Nodamura Virus B2 Protein
To solve this, Dr Pierre Maillard and Dr Raul Yusef Sanchez David of the Blizard Institute identified a solution in a viral protein called NoV B2. This protein is known to suppress RNA interference, one of the primary mechanisms cells use to restrict double-stranded RNA.
By adding NoV B2 to the saRNA, the researchers reduced the extent to which cells restricted the vaccine. This allowed the cells to produce far more of the intended protein without undermining the vaccine’s ability to stimulate the immune system. The study, titled Tuning intracellular immunity by Nodamura virus B2 protein enhances self-1 amplifying RNA activity
, confirms these results in both regular cells and stem cells.
“Our findings identify a strategy to overcome a fundamental barrier limiting self-amplifying vaccines. If this translates successfully in vivo, it could open new possibilities for vaccine design as well for gene therapies and cancer treatment.”
Dr Pierre Maillard, Senior Lecturer in antiviral immunity at Queen Mary University of London
Applications in Cancer and Gene Therapy
The ability to boost protein production in the lab suggests the technology could extend far beyond traditional vaccinations.
- Cancer Immunotherapy: The development of more potent cancer vaccines.
- Gene Therapy: Making treatments safer and more affordable.
- Protein Replacement: Transforming therapy from a cycle of repeated infusions to a system where the patient’s own body generates the medicine.
Funding Shifts and Commercialization
This discovery arrives during a period of volatility for mRNA research funding. The global scientific community has expressed widespread concern following a $500m cut to mRNA vaccine research announced by the United States.
Against this backdrop, the Queen Mary team is moving toward practical application. They are currently collaborating with Queen Mary Innovation, the university’s technology transfer arm, to secure a commercial partner capable of developing the technique for clinical use.