Health
RNA researcher on the basics of how mRNA vaccines are made and work
In light of recent wins for mRNA vaccine makers, UCSC RNA Center Co-Director Jeremy Sanford describes the versatility of the mRNA platform and how it quickens vaccine production
Professor Jeremy Sanford chairs the Department of Molecular, Cell, & Developmental Biology and co-directs the RNA Center at UC Santa Cruz.
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The U.S. Food and Drug Administration’s approval of the first mRNA influenza vaccine on August 5 was not only a triumph for public health, but also for the science behind it. Called mFLUSIVA, the vaccine made by Moderna had faced strong headwinds in the form of an initial refusal by the F.D.A. to review the application, as well as mistrust of mRNA vaccines by some who seemed swayed more by misinformation campaigns than scientific evidence.
Americans have largely learned to live with the flu, but it still takes a serious toll. For the 2024-25 flu season—the most recent one fully assessed by the U.S. Centers for Disease Control and Prevention (CDC)—the agency deemed its severity as “high,” with an estimated 45,000 deaths that season. Conversely, the CDC reported that flu vaccines prevented about 10 million illnesses and 12,000 deaths that same season.
Then on August 19, drugmaker Merck announced with Moderna that a late-stage trial of their experimental melanoma vaccine slowed both the return and spread of cancer in the body. And yet, mRNA vaccines remain murky in the minds of many. So Professor Jeremy Sanford, chair of the Molecular, Cell, & Developmental Biology Department at UC Santa Cruz, explained how mRNA vaccines work, how they can reach patients faster than conventional vaccines, and what approval of mFLUSIVA means for the development of mRNA vaccines for other illnesses going forward.
How do mRNA vaccines work?
Sanford: mRNA vaccines deliver a short-lived genetic blueprint, called messenger RNA (mRNA), into our cells. The mRNA instructs cells to temporarily produce a single protein from the virus or pathogen—known as an antigen—which is recognized by the immune system. This stimulates the production of antibodies and immune memory, preparing the body to respond quickly if it later encounters the actual pathogen.
Importantly, the mRNA does not enter the cell nucleus or alter a person’s DNA, and it is naturally degraded within a short period of time.
How effective are mRNA vaccines compared to conventional vaccines?
Sanford: The effectiveness of any vaccine depends on the disease, the population being vaccinated, and how well the vaccine matches circulating strains. In the Phase 3 trial supporting F.D.A. approval of Moderna’s mFLUSIVA vaccine, the company reported that the vaccine reduced influenza cases more effectively than a licensed comparator vaccine in adults aged 50 years and older, with particularly strong performance in adults aged 50–64.
One of the major advantages of mRNA technology is speed. Once the genetic sequence of an emerging pathogen is known, researchers can rapidly design an mRNA vaccine encoding the desired antigen. In contrast, conventional influenza vaccines often require months of manufacturing using egg- or cell-based production systems. mRNA vaccines rely on the body’s own cells to produce the antigen, generating an immune response without exposing the recipient to the complete virus.
What does the approval mean for mRNA vaccines for other illnesses going forward?
Sanford: F.D.A. approval of an mRNA influenza vaccine is an important milestone because it demonstrates that the mRNA platform can be successfully applied beyond COVID-19. It reinforces the versatility of RNA-based medicines and provides additional confidence that this technology can be adapted for a wide range of applications.
Looking ahead, researchers are developing mRNA-based therapies for infectious diseases, cancer immunotherapy, and some rare genetic disorders. Continued investment in both basic RNA biology and translational research will be essential for improving the precision, durability, and effectiveness of these therapies.
At the UCSC RNA Center, our research focuses on many of the fundamental processes that make RNA therapeutics possible—including RNA structure, RNA modifications, RNA translation, and RNA-based diagnostics. Advances in these basic areas provide the scientific foundation for the next generation of RNA medicines.
Are you familiar with Moderna’s mRNA flu vaccine?
Sanford: Moderna’s mFLUSIVA vaccine uses the same general mRNA platform that was successfully deployed during the COVID-19 pandemic. Instead of encoding the SARS-CoV-2 spike protein, however, it encodes the influenza virus hemagglutinin (HA) proteins from influenza A and B strains—the major viral proteins recognized by protective antibodies.
One noteworthy aspect is the scale of the clinical evaluation. The Phase 3 trial enrolled more than 40,000 adults, providing a robust assessment of the vaccine’s safety and effectiveness before F.D.A. approval.
Could you explain the basis for general skepticism some have about mRNA vaccines?
Sanford: New medical technologies often generate questions, and mRNA vaccines were introduced during a global pandemic when information—and misinformation—spread rapidly. Early questions about safety, long-term effects, and the speed of vaccine development were understandable and were addressed through extensive clinical trials and ongoing safety monitoring.
At the same time, many false claims circulated that were not supported by scientific evidence. These included assertions that mRNA vaccines alter human DNA, contain tracking devices, or affect fertility. These claims have been carefully evaluated and are not supported by decades of molecular biology research, clinical trial data, or post-authorization safety monitoring.
One of the continuing challenges for scientists and physicians is communicating complex science clearly so that the public can distinguish evidence-based information from misinformation.
What is the potential for the science that results in mRNA vaccines?
Sanford: The potential extends well beyond vaccines for infectious diseases. Because mRNA can instruct cells to temporarily produce almost any protein, it has broad applications across medicine.
Researchers are developing mRNA therapies to replace missing or defective proteins in certain rare genetic diseases, for personalized cancer vaccines that train the immune system to recognize an individual’s tumor, and for treatments that stimulate immune responses against difficult-to-treat cancers. Clinical trials are already underway for several cancers, including glioblastoma and pancreatic cancer.
More broadly, the success of mRNA vaccines has accelerated an entire field of RNA medicine. As our understanding of RNA biology continues to improve, we are likely to see an expanding range of RNA-based therapeutics over the coming decade.
Sanford co-directs the UCSC RNA Center, which hosted its first major international conference on campus, the RNA Futures Meeting, from August 18 to 21.