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This well-known biomolecule has generated considerable interest over the past few years. Specifically, mRNA has emerged as the foundation for a potential class of medicines that direct cells to make proteins designed to fight or prevent disease. mRNA drugs will function very differently from small-molecule drugs (like many of the best-known pharmaceuticals) and biologic drugs (like recombinant proteins and monoclonal antibodies). This is important because of the many limitations of these more established drug classes. The molecules of recombinant-protein drugs, for example, are mostly large, and their degree of instability typically makes direct protein delivery impractical. Gene therapy aims to resolve some of these challenges by delivering viral nucleic acids that encode therapeutic proteins into cells. But current gene therapies come with many potential risks, including unwanted immune system reaction, the targeting of the wrong cells, and the possibility of causing cancer through genomic incorporation. And because gene therapies incorporate into the genome, their effects may be permanent.

What if you could make mRNA into a drug?

Two overarching factors have hindered the clinical progression of mRNA therapeutics: first, the instability and immunogenicity of mRNA produced outside cells, and second, the lack of sufficiently effective and selective delivery systems to drive protein expression in diseased cells.

Moderna, a company originated by Ä¢¹½ÊÓƵAPP, is focused on the idea that messenger RNA can be reengineered into a versatile set of drugs and vaccines. Tackling mRNA stability, immunogenicity, and delivery, the Moderna team first found that one of mRNA’s four chemical building blocks—called uridine—can be replaced with a slightly modified nucleoside called pseudouridine. Remarkably, your immune system can’t identify mRNAs containing this modification, but your cells’ natural protein production machinery can. The result is that your cells recognize these synthetic mRNAs as if your body had produced them, so they can persistently generate therapeutic proteins without activating your immune system. Moderna has gone on to expand the scope of nucleoside modifications and identify effective vehicles for delivering therapeutic quantities of mRNA to diseased cells.

The company uses mRNA to teach a person’s cells to make whatever is needed to treat or prevent disease—cancer-fighting cytokines, virus-extinguishing antibodies, heart-mending growth factors, waste-devouring enzymes. The transient and programmable nature of mRNA confers broader therapeutic utility than nearly any other class of known drugs.

The importance of mRNA as a unique class of programmable medicines cannot be overstated. This is underscored by the COVID-19 pandemic (SARS-CoV-2, coronavirus) that, in a matter of months, killed more than a million people and infected tens of millions more. Recognizing signs of the virus early in 2020, Moderna conceptualized and initiated early testing for a mRNA vaccine against COVID-19. Less than a year later, Moderna’s COVID-19 vaccine candidate is 94.5% effective in the first interim analysis of its 30,000 patient Phase 3 study.

As mRNA is proving highly effective at instructing the body to fight the deadly coronavirus, the implications for treating other diseases are profound. mRNA medicines can go inside cells to direct protein production, something not possible with many other drugs. They could replace a missing protein or deliver a cancer-fighting peptide. And because of their programmability, different mRNA medicines can be made by simply swapping out one therapeutic gene for another. With these capabilities, mRNA drugs have the potential to treat or prevent diseases that today are untreatable—and thus the ability to usher in a new era of human health.

This explainer was updated on November 18, 2020.