Daily RC Article 295

The Evolution of mRNA: From Concept to COVID-19 Savior

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Synthetic mRNA, the ingenious technology behind the Pfizer-BioNTech and Moderna vaccines, might seem like a sudden breakthrough, or a new discovery. One year ago, almost nobody in the world knew what an mRNA vaccine was, for the good reason that no country in the world had ever approved one. Months later, the same technology powered the two fastest vaccine trials in the history of science. Like so many breakthroughs, this apparent overnight success was many decades in the making. More than 40 years had passed between the 1970s, when a Hungarian scientist pioneered early mRNA research, and the day the first authorized mRNA vaccine was administered in the United States, on December 14, 2020. In the interim, the idea’s long road to viability nearly destroyed several careers and almost bankrupted several companies.

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The dream of mRNA medicines persevered in part because its core principle was tantalizingly simple, even beautiful: The world’s most powerful drug factory might be inside all of us. People rely on proteins for just about every bodily function; mRNA—which stands formessenger ribonucleic acid—tells our cells which proteins to make. With human-edited mRNA, we could theoretically commandeer our cellular machinery to make just about any protein under the sun. You could mass-produce molecules that occur naturally in the body to repair organs or improve blood flow. Or you could request our cells to cook up an off-menu protein, which our immune system would learn to identify as an invader and destroy.

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In the case of the coronavirus that causes COVID-19, mRNA vaccines send detailed instructions to our cells to make its distinctive “spike protein.” Our immune system, seeing the foreign intruder, targets these proteins for destruction without disabling the mRNA. Later, if we confront the full virus, our bodies recognize the spike protein again and attack it with the precision of a well-trained military, reducing the risk of infection and blocking severe illness. But mRNA’s story likely will not end with COVID-19: Its potential stretches far beyond this pandemic. This year, a team at Yale patented a similar RNA-based technology to vaccinate against malaria perhaps the world’s most devastating disease. Because mRNA is so easy to edit, Pfizer says that it is planning to use it against seasonal flu, which mutates constantly and kills hundreds of thousands of people around the world every year. The company that partnered with Pfizer last year, BioNTech, is developing individualized therapies that would create on-demand proteins associated with specific tumors to teach the body to fight off advanced cancer. In mouse trials, synthetic-mRNA therapies have been shown to slow and reverse the effects of multiple sclerosis. “I’m fully convinced now even more than before that mRNA can be broadly transformational,” Özlem Türeci, BioNTech’s chief medical officer said. “In principle, everything you can do with protein can be substituted by mRNA.” In principle is the billion-dollar asterisk. mRNA’s promise ranges from the expensive-yet-experimental to the glorious-yet-speculative. But the past year was a reminder that scientific progress may happen suddenly, after long periods of gestation.