A new study led by scientists at Queen Mary University of London describes a way to overcome a cell’s natural defenses against self-amplifying RNA vaccines. According to details provided in a new Nature Communications paper, adding a viral protein dubbed NoV B2 helps overcome this issue, while preserving saRNA’s ability to stimulate the immune system. 

According to details provided in the paper, which is titled “Tuning intracellular immunity by Nodamura virus B2 protein enhances self-1 amplifying RNA activity,” found that adding this protein, which is known to suppress RNA interference, reduced the extent to which the cells restrict saRNA, allowing it to provide far more of the intended protein in both stem cells and regular cells. It addresses a major challenge with saRNA vaccines that hampered their application in gene therapies, cancer immunotherapies, and protein replacement therapies. 

Most people are familiar with mRNA-based vaccines because of the Covid-19 pandemic. Since then scientists have worked on developing saRNA which replicates within host cells. The goal is to use the technology to develop vaccines and therapies that provide longer-lasting protection at lower doses that are safe and affordable.

Specifically, during the self-replicating process, saRNA generates double-stranded RNA which triggers cells’ anti-virus defenses. This makes the saRNA less stable, less able to replicate, and less able to instruct cells to produce the protein that trains the immune system. To date, this has limited the effectiveness of saRNA vaccines. But this development could help scientists develop effective saRNA vaccines that work at lower doses and could be rolled out further and faster than has been possible. 

According to Pierre Maillard, PhD, senior lecturer in antiviral immunity at Queen Mary University of London, and one of the authors on the study, “our findings identify a strategy to overcome a fundamental barrier limiting self-amplifying vaccines” and “if this translates successfully in vivo, it could open new possibilities for vaccine design as well for gene therapies and cancer treatment.”