Miraculous Molecule: What Comes Next for mRNA?

In these opening days of 2022, there’s no denying that the Omicron variant has emerged as a formidable foe, washing over communities around the world and leaving a wide swath of infection and misery in its wake.?

It’s not how we’d hoped to begin the new year, to be sure; but nearly two years into this global pandemic, I’m thankful that we’re better equipped to protect ourselves today than ever before. Though Omicron has proven adept at evading antibodies, early studies?indicate ?that receiving two doses of COVID-19 vaccine, along with a booster shot, dramatically reduces the risk of severe illness. What’s more, as we faced the possibility of an Omicron-fueled surge back in December, both Pfizer and Moderna?said ?they could quickly produce a new version of their vaccines, tailored for fighting the new variant, if protection from the original formulation fell short.?

This agility is possible thanks to a powerful new tool in our evolutionary arms race against viruses. mRNA technology, the same used by Pfizer and Moderna, enables us to quickly create effective vaccines and recalibrate them as needed for emerging variants — and that’s only scratching the surface of this molecule’s medical possibilities. Beyond COVID-19 vaccines, mRNA holds significant potential for protecting humans against a wide array of other stubborn viruses, and even targeting other diseases, such as cancer.?

But to truly appreciate the future of mRNA, it’s essential to understand its past.

Developing mRNA technology

Messenger ribonucleic acid, known as mRNA, was first identified in 1961. As its name suggests, mRNA delivers information — in this case, instructions to cells on how to make proteins that are essential to our body’s functions. The scientific community quickly realized that customized versions of this molecule could have significant medical applications. But it took years for researchers to devise a synthetic mRNA molecule and even more time to find a way to successfully introduce the molecule into human cells. By 2019, scientists were close to perfecting the platform, conducting clinical trials for mRNA vaccines for rabies, Zika virus, and influenza, among other illnesses. When the pandemic struck, the technology was ready.

Creating COVID-19 vaccines

mRNA vaccines?work ?by instructing our cells to produce a harmless piece of a virus protein—in the case of SARS-CoV-2, the spike protein—which then trains our body to produce an immune response. The protein essentially acts as a stand-in for the virus, helping our immune system to quickly recognize it and fight off infection if exposed.

As genetic mutations of the virus—and its signature protein—emerge, scientists need only to adjust the mRNA molecule’s “instructions” to formulate a new version of their vaccine —?a process that can be accomplished in a matter of weeks.

By contrast, traditional vaccines rely on using an inactivated or weakened version of a virus to trigger an immune response; and it can take months for scientists to isolate the virus, grow it, and create the sample they need for clinical testing.

The mRNA method was expected to be faster and more flexible than previous technology, but it was less certain how the efficacy of these vaccines would compare. To the great benefit of people around the globe, data from clinical trials, and later in the general population, have decisively demonstrated their protective power against the virus causing COVID-19.

Bright future for mRNA?

mRNA technology is now in consideration for many potential uses. For example, scientists are exploring developing a so-called universal vaccine. With this method, they would package together several distinct mRNA molecules in one vaccine, coding for proteins from a virus and all its known variants. mRNA could also be leveraged for such innovations as personalized cancer treatments, where a custom mRNA molecule is created, based on the genetic profile of a tumor, to reinforce an individual’s immune response.

The success of mRNA vaccines has also galvanized scientists’ work with other types of RNA by demonstrating so decisively what these molecules are capable of. Researchers — including at Stanford Medicine — are conducting in-depth studies with implications for how we understand everything from?human aging ?to?brain development, ?in addition to the immune system. The possibilities are boundless, and I’m looking forward to watching them unfold. I’m also inspired by the history of this innovation. It’s a testament to the importance of basic science research — investigations that provide the essential, foundational knowledge upon which all novel therapeutics, interventions, and diagnostics are built.?

Just last month, I?appeared ?before the U.S. House of Representatives Committee on Energy and Commerce’s Subcommittee on Health to discuss the essential role of this early-stage research. I’m proud that it thrives here at Stanford Medicine, and I’m heartened that it continues to be a priority for federal support.

Here are some resources for further reading about the history and future of mRNA research:

The Tangled History of mRNA Vaccines ?This comprehensive piece from?Nature?provides an in-depth look at the history of mRNA research.

Study Shows Why Second Dose of COVID-19 Vaccine Shouldn’t Be Skipped ?Stanford Medicine professor Bali Pulendran led research that investigated how the Pfizer/BioNTech COVID-19 vaccine works on a molecular level.

Now proven against coronavirus, mRNA can do so much more ?This piece from CNN highlights areas of potential for mRNA technology.

First, impressive vaccines for COVID. Next up: The Flu ?In this article, the?New York Times?explores the history of flu vaccines and how mRNA could alter the future.