Ars Technica
The world of biomedicine has developed a lot of technology that seems a small step away from science fiction, but the public is not much aware of it. However, one such technology, mRNA-based vaccines, was a major exception, as much of the public followed the development of the technology as an important step to emerge from the worst of the pandemic and then received the vaccines en masse.
mRNA technology has many potential applications outside of COVID, and we talked a bit about that during the “Beyond COVID: What Does mRNA Technology Mean for Disease Treatment?” panel at last week’s Ars Frontiers event. We’ve archived the panel on YouTube; if you want to focus on the discussion of mRNA therapies, you can start at the 1 hour and 55 minute mark.
mRNA is a nucleic acid molecule that instructs the cell to make specific proteins. When used as vaccines, the instructions call for a protein produced by a pathogen, such as a virus. “It helps put up a wanted poster for the immune system,” was how Nathaniel Wang, co-founder and CEO of Replicate Bioscience, put it.
The production of a wanted poster is no different from other vaccines. “mRNAs is just the vessel, it’s the means of transport,” says Karin Bok of the National Institutes of Health. “So let’s say you have your sandwich for lunch — mRNA is the bread you choose to deliver that sandwich.” Where RNA differs is how easy it is to work with. Bok said that since the mRNA is synthetic, it avoids many of the potential safety precautions that need to be taken when the vaccine is produced in cells. (Bok is the director of Pandemic Preparedness and Emergency Response at NIH’s Vaccine Research Center.) This means we can get a vaccine into safety testing quickly and potentially test alternative vaccines in parallel.
That ease of use also affects production. “You don’t have to recreate a production process for flu versus COVID-19 versus Epstein-Barr virus,” Wang said. “You just change the sequence in the RNA itself, but the way you make and purify that material is the same, which is why it’s so much faster.”
Beyond speed
Speed of development has some additional advantages. Bok cited seasonal vaccines, such as the flu (and possibly COVID in the future), as a big beneficiary. As the testing and manufacturing process moves faster, we can wait a few extra months to collect additional data before committing to a specific formulation for the Vaccine of the Year. Furthermore, Bok suggested that we will use mRNAs for other diseases, but which will depend on an analysis of the specific disease and whether mRNA can provide what is needed to generate lasting immunity.
Wang, for his part, is excited about technologies under development (he called them “mRNA 2.0”) that could produce more proteins from each RNA molecule and contain signals that stimulate the immune response. This, he suggested, could reduce the required vaccine dose by as much as 1,000 times, making production even easier.
That could be good news for applications beyond vaccines. Therapies such as those for autoimmune diseases and diabetes may be based on protein injections, often done daily. But with mRNAs, we can get our cells to produce the therapies themselves. Wang said work is underway to develop mRNA-like molecules that could drive expression for weeks or even months, potentially eliminating the need for daily injections.
Looking further into the future, Wang said people are working on so-called “cancer vaccines,” which use proteins to restore the immune response to cancer cells. mRNA, he suggested, was an obvious candidate for use in this work.
However, all of these applications depend on the public being comfortable with the continued use of mRNA, which has generated considerable suspicion in some circles following the COVID vaccine rollout. Bok attributed that in part to the speed aspect of Project Warp Speed, though she emphasized that “we’re only betting money; we’re not betting on safety.” But she also acknowledged that there is a longstanding mistrust of vaccines in many societies.
“I think our R&D enthusiasm should go hand in hand with how we can build confidence in vaccines, but also in mRNA vaccines, which is a fantastic new technology that we can use for many, many infectious diseases that we don’t know about. vaccines,” Bok said. She and Wang stressed that transparency and authenticity will be key to building trust.
Still, the fact that we need to restore confidence is a sign of how successful this technology has been compared to how it was pre-COVID. “I think sometimes it’s hard to remember something before the pandemic, but people were willing to take RNA technologies behind the shed and shoot at it,” Wang said. “There were real questions about whether it could ever be scaled up, whether it would ever become commercially deployable, whether there would be fundamental security questions. A resounding yes, it’s a scalable technology, it can be manufactured, it can be safe and deployable. “
