Will mRNA Technology Transform Medicine Beyond COVID-19?

By: Jennifer Walker-Journey  | 

moderna vaccine
The Moderna and Pfizer mRNA COVID-19 vaccines have helped significantly reduce the number of cases of COVID-19 since they were first approved for emergency use. Dinendra Haria/SOPA Images/LightRocket via Getty Images

For decades, researchers have dreamed about harnessing the power of genetic technology to prevent or treat a range of diseases. A synthetic version of a molecule in the human body known as messenger RNA (ribonucleic acid), or mRNA, held that promise.

Just how to make it work presented daunting challenges that much of the science community thought was a mountain too high to climb.

But a handful of researchers didn't give up. They spent years trying to solve the mystery of mRNA. Then, just like a made-for-TV movie, they cracked the code just in time to save the world from the deadly coronavirus pandemic.

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mRNA on a Mission

mRNA vaccines work by delivering instructions to cells that empower them to produce antigens and become the body's own antibody-producing factory. But to understand the technology even better and how it is being used to protect us from COVID-19, you first need to understand proteins.

Proteins are often referred to as the building blocks of life. They are essential for the structure, function, and regulation of the body's tissues and organs. Every cell in the human body contains tens of thousands of distinct proteins made up of several amino acids that attach to each other to create chains of varying lengths that fold into various shapes. Protein shape has a great deal to do with protein function.

For example, some regulate specific physiological processes, such as growth, development, metabolism and reproduction. Some proteins act as biological catalysts to help the body build muscle, destroy toxins and break down food particles during digestion. Others serve the immune system as antibodies that can fight infections viruses and bacterial pathogens.

Cells are assigned their amino acid sequence, and thus told the function of their protein via the body's messenger RNA, or mRNA.

Think of this process like a spy mission. mRNA hands the cell instructions to make a certain protein. Once the cell makes its protein, the cell destroys the instructions and then goes to work manufacturing that specific protein.

coronavirus
This graphic shows the structure and anatomy of the coronavirus, including its proteins, ribosomes, RNA and envelope.
OSweetNature/Shutterstock

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Seemingly Endless Possibilities of mRNA Technology

A few researchers began to wonder: What if science could develop a synthetic mRNA with a specific coding sequence that could be delivered to the body and instruct cells to create any type of protein — growth agents to repair damaged tissues, enzymes to cure rare diseases or even antibodies to protect against infection.

In 1990, a group of University of Wisconsin researchers actually pulled off making a synthetic mRNA and tested it in laboratory mice. The problem was that synthetic mRNA was sensitive to the mice's defenses and was destroyed before ever reaching the target cell to deliver the coded message, says Paul Goepfert, M.D., professor of medicine at the University of Alabama at Birmingham and an expert in vaccine design. Many in the scientific world saw this as a fatal flaw and turned their attentions elsewhere.

But two University of Pennsylvania researchers, Katalin Karikó, Ph.D., and immunologist Drew Weissman, M.D. Ph.D., still believed in the opportunities synthetic mRNA held. They set out to find a way to make mRNA more stable. In 2005, after a decade of painstaking research, they discovered that they could use tiny balls of fat called lipid nanoparticles, or LPNs, to protect the synthetic mRNA. This gave the fragile molecule stealth-like qualities that enabled it to travel outside the immune system's radar.

In the years that followed, researchers would explore the possibilities of mRNA using this new technology. In 2010, Cambridge, Massachusetts-based pharmaceutical and biotechnology company Moderna Inc., was founded to focus specifically on vaccine technologies based on mRNA. The name "Moderna" literally comes from combining the words "modified" and "RNA."

In 2008, German-based BioNTech, short for Biopharmaceutical New Technologies, was founded to develop pharmaceutical cancer immunotherapy candidates using mRNA technology. In 2018, the company partnered with U.S.-based Pfizer Inc. to develop mRNA-based flu vaccines.

And then the world was hit by a global pandemic. Researchers everywhere began directing all their efforts toward developing a vaccine for coronavirus.

mrna vaccine
This diagram shows an encapsulated mRNA vaccine from a viral spike protein (developed from COVID-19 or SARS-CoV-2) and how its work for immune response.
BigBearCamera/Shutterstock

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How Did mRNA Vaccines Get Approved So Fast?

Viruses cannot reproduce on their own. They need host cells that they infect to begin the process, which in cases of infectious viruses, makes people sick. For an mRNA vaccine to work, researchers needed to know which protein the virus was using as its host cell. And for that, they needed to crack COVID-19's genetic code. This process was simplified because COVID was similar to two other coronaviruses that had previously infected humans — MERS and SARS.

By Dec. 31, 2020, when China first admitted the cluster of pneumonia-like viruses, Chinese researchers there were already working to identify the virus' genetic code. About two weeks later, Jan. 12, 2020, they released the gene sequencing data. This gave researchers everywhere the ammunition to start on a vaccine.

"We knew that the spike protein was the Achilles' heel," Goepfert says.

From there, vaccine development began to move swiftly. "mRNA vaccines are amenable to very rapid development. We got kind of lucky from that aspect," Goepfert says. "A week later, Moderna and Pfizer made their vaccines." The companies were then able to propel ahead of drug companies developing traditional vaccines, and move quickly into animal testing and, shortly thereafter, human trials began.

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Are mRNA Vaccines as Effective as Traditional Vaccines?

Both Moderna and Pfizer/BioNTech vaccines are performing surprisingly well. Studies have shown that a full double dose of Pfizer's or Moderna's vaccine provides 95 percent and 94 percent protection against the original virus, respectively.

Yet barely half of all Americans are fully vaccinated.

"One of the reasons for vaccine hesitancy is that people have this misunderstanding that [mRNA COVID vaccines] were developed so quickly and that, in doing so, we skipped safety evaluation, which is not true at all," Goepfert says.

"This vaccine has been tested on incredible numbers of people and it actually underwent the normal safety testing of any products. And now that it's under Emergency Use Authorization we have millions more safety data — actually more than any other product that we've had for a vaccine."

These mRNA vaccines work so well because they induce multiple arms of defense in the immune system, Goepfert says. "They induce the neutralization of antibodies, which I think of as spears because they can knock out the virus before you even get infected. They induce functional antibodies, which utilize cells to be more effective. And they induce T-cell responses — both helper and killer cell responses — which are extremely important. T-cells help prevent severe disease and death." A neutralizing antibody (NAb) is an antibody that defending cells from pathogens.

Traditional vaccines also create neutralizing antibodies and induce antibody responses, but "they don't do the T-cell response as well," he says.

covid vaccine
A woman displays a victory sign while she receives the first dose of a COVID-19 mRNA vaccine June 22 in Guwahati, India. India is recovering from a severe outbreak of the delta variant where more than 7,300 people died in 24 hours in June from COVID-19.
Anuwar Ali Hazarika/Barcroft Media via Getty Images

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The Future of mRNA Vaccines

So what does the future hold for mRNA technology? This is likely just the beginning. In fact, in 2017, two clinical trials were already underway to test mRNA vaccines against several infectious diseases, including HIV, influenza, Zika and rabies — and then COVID-19 hit.

A team at MD Anderson led by Scott Kopetz, M.D., Ph.D., is already using mRNA on colorectal cancer in a Phase II clinical trial to test whether the technology could prevent the cancer from recurring.

"mRNA vaccines can be used to target almost any pathogen," John Cooke, M.D., Ph.D., medical director of the RNA Therapeutics Program at the Houston Methodist Research Institute, said in a press statement for the Association of American Medical Colleges. "You put in the code for a particular protein that stimulates an immune response. It's essentially unlimited."

That means scientists think diseases like malaria, tuberculosis, hepatitis B and cystic fibrosis could all be prevented in the future with mRNA vaccines.

"These vaccines are remarkable," Goepfert says. "Even in older adults, they work really, really well, which is unusual for most any vaccine that we have. So that's just remarkable."

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Originally Published: Jun 22, 2021

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