mRNA technology topped MIT Technology Review's 2021 "10 Breakthrough Technologies" list, with the significant recognition that mRNA COVID-19 vaccines achieved ~95% efficacy despite never having been clinically applied before, potentially transforming medicine. Although mRNA's journey from discovery to market took just 60 years—relatively brief in pharmaceutical terms—it involved countless researchers overcoming numerous technical hurdles.

mRNA was first discovered in 1961. The prototype for mRNA therapy dates to 1990, when the Jon Wolff laboratory at the University of Wisconsin first reported that in vitro-transcribed (IVT) mRNA injected into mice expressed active protein in a dose-dependent manner, eliciting an immune response. While this demonstrated mRNA's vaccine-like potential, progress was slow due to two major limitations: (1) mRNA's instability and rapid degradation—it is one of the shortest-lived RNA species, with a half-life of minutes to hours; and (2) the lack of safe, effective delivery vehicles capable of protecting mRNA from rapid degradation and delivering it into the cytoplasm.

As Dr. Katalin Karikó of the University of Pennsylvania said: "mRNA therapy could become an alternative to DNA therapy. Unfortunately, due to technical limitations, no one was interested at the time. But the direction was there, and someone had to rise to the challenge."

In 2005, after years of difficult research, Karikó and Dr. Drew Weissman discovered that the key to mRNA's immune response lay in uridine—by simply modifying uridine nucleotides to pseudouridine, they could evade immune surveillance, solving the immune response problem. They received numerous awards including the 2021 Lasker Award.

The exploration of delivery technology also continued. Since the 1960s, scientists had been studying how to encapsulate and deliver large molecules. Dr. Pieter Cullis of the University of British Columbia began researching how to get mRNA into cells without degradation in the 1980s, discovering that anticancer drugs could diffuse and remain in liposomes, which then crossed tumor vasculature to deliver drugs into cells. Through continuous optimization, LNPs gradually became applicable for nucleic acid delivery, enabling large-scale human clinical studies. In April 2022, Cullis received the Gairdner Award—often called Canada's "Nobel Prize."

With LNP delivery and sequence modification technologies maturing, the mRNA industry gained momentum. In 2018, the FDA approved the first LNP-delivered nucleic acid drug Patisiran—the world's first siRNA drug. In the fight against COVID-19, mRNA therapy succeeded: in December 2020, the first mRNA vaccine BNT162b2 received EUA in the U.K., and in August 2021, it received FDA approval. mRNA research entered a new phase of explosive growth, driving the entire drug development field in new directions.

As Dr. Cullis said when faced with recognition: "I never imagined that my curiosity would play a key role in vaccine development, yet these vaccines are now tangibly benefiting billions of people worldwide."