Boosting self-amplifying RNA vaccine expression

Background

mRNA-based vaccines were central to getting us out of the Covid-19 pandemic. Unlike conventional vaccines, which use a low dose of the virus to build immunity, RNA vaccines tell your cells to produce a protein which teaches your body how to fight the virus.

Since then, scientists have been working on self-amplifying mRNA vaccines (saRNA) which replicate within host cells. These next-generation vaccines could provide longer-lasting protection at lower doses, meaning vaccines could be rolled out further and faster than was previously imaginable.

The benefits go beyond pandemic protection. saRNA vaccines hold great promise as a novel strategy in gene therapy, cancer immunotherapy, and protein replacement therapies.

The Problem

In the process of self-replicating, saRNA generates double-stranded RNA (dsRNA) which triggers cells’ anti-virus defences. 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. It’s a major flaw limiting how effective an saRNA vaccine can be.

Invention: Benefits and Application

Dr Pierre Maillard and Dr Raul Yusef Sanchez David, scientists at Queen Mary University of London’s Blizard Institute, found that adding NoV B2 (a protein known to suppress RNA interference, one of the cell’s natural defences against this double-stranded RNA) reduces the extent to which cells restrict the saRNA, allowing it to produce far more of the intended protein in both stem cells and regular cells. Crucially, it does so without undermining saRNA’s ability to stimulate the immune system.

The innovation opens new possibilities in gene therapy, cancer immunotherapy, and protein replacement therapies.

If translated successfully, this technology could make gene therapy safer and more affordable; make cancer vaccines more potent; and turn protein-replacement therapy from a process of repeated infusions to one in which the patient’s body generates its own medicine.

The research is published in Nature Communications: Tuning intracellular immunity by Nodamura virus B2 protein enhances self-amplifying RNA activity

We’re looking for a commercial partner to help develop the technique for clinical use.