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UBC professor Dr. Pieter Cullis.Paul Joseph/Courtesy of manufacturer

When Pieter Cullis rolled up his sleeve last March to receive his first dose of the Pfizer-BioNTech vaccine for COVID-19, he couldn’t help but remark on what the moment meant for him as a scientist.

“You know,” he told the nurse who was administering the jab, “I actually had something to do with making this vaccine.”

She responded by shooting him a glance that was more odd than awed.

“Like I was from outer space,” Dr. Cullis recalled.

Now the University of British Columbia professor and co-founder of Acuitas Therapeutics in Vancouver has earned a little more recognition after being named a co-winner last week of the 2021 Prince Mahidol Award for medicine. The award, which comes with US$100,000, is one of the first high-profile international science prizes to acknowledge the pioneers behind mRNA vaccines – the most effective defence against COVID-19.

Dr. Cullis is sharing the prize with Katalin Kariko, the senior vice-president at BioNTech, based in Mainz, Germany, and Drew Weissman, the director of vaccine research at the University of Pennsylvania. His co-winners are credited with figuring out how to engineer messenger RNA – a molecule that carries instructions for making proteins – for use as the active ingredient in vaccines. The COVID-19 vaccines developed by BioNTech and by Moderna, based in Cambridge, Mass., both rely on the discovery.

Dr. Cullis played a different role. It was through his work over many years that vaccine makers had a way to encase the fragile messenger RNA molecules inside a lipid bubble, or “nanoparticle,” which protects RNA from degradation and allows it to penetrate cells. The system is essential for the vaccines to work.

In announcing the prize, the Prince Mahidol Award Foundation in Thailand said Dr. Cullis’s achievement not only made the vaccines possible, it has opened the door to “the prevention and treatment of many diseases in the future.”

Alan Bernstein, the president of CIFAR, a Toronto-based research funding organization, and a member of Canada’s COVID-19 vaccine task force, called Dr. Cullis’s contribution “a great example of the power of fundamental science in the service of humanity.” In addition to enabling the mRNA revolution in vaccine development, he said, the technology would likely find further applications in cancer research, among other areas.

For Dr. Cullis, such exciting possibilities were hardly on the horizon in the 1970s when he completed his PhD in experimental physics at UBC before deciding that the problems researchers were tackling in the life sciences looked far more stimulating.

During postdoctoral work at Oxford University, he became fascinated with the characteristics of lipid membranes – the double-layered fatty sheaths that enclose living cells and various cell components. He was particularly intrigued with the fact that some membranes are markedly different on their inner and outer surfaces, featuring a diverse array of lipids on either side.

“I got interested in why there were so many different lipids and what they were all doing,” he said.

While studying the question, he learned to wrap lipid membranes around molecules in order to probe the chemical properties of the membranes’ inner surfaces. From there it was a short conceptual step to thinking about packing a drug inside a lipid in order to help get it to where it was needed in the body.

By then he was back at UBC and running his own lab. He had built a team of young researchers and was exploring how to design lipids for drug delivery. What followed was more than two decades of basic research in the lab combined with a succession of startup companies and partnerships to develop applications. At first, the team’s focus was on cancer drugs, but by 2000 work had shifted toward a new medical frontier: gene therapy.

Dr. Cullis said a crucial period began in 2005 when he and his colleagues teamed up with Massachusetts-based Alnylam Pharmaceuticals to develop an RNA drug that suppresses the action of a faulty gene in liver cells, the cause of a condition known as amyloidosis. The size and chemical properties of RNA are far different than the cancer drugs the team had previously worked with. That meant the lipid packaging system had to be rebuilt from the ground up.

The collaboration succeeded and pointed the way to an even bigger challenge. If a short piece of RNA could be delivered to interrupt a biological process, why not a larger piece of messenger RNA to introduce a new biological process?

By this point Dr. Cullis had already co-founded Acuitas to develop lipid nanoparticle pharmaceuticals. In 2014 the company received an e-mail from Dr. Weissman, who was working with BioNTech on messenger RNA vaccines and needed a delivery system. More years of work followed, and by late 2019 Pfizer had also joined the project to make an mRNA influenza vaccine using lipid nanoparticles.

Then the pandemic hit. Virtually overnight, the entire effort was redirected toward COVID-19. By the spring of 2020, the Pfizer-BioNTech vaccine was in clinical trials. Meanwhile, Moderna, which had previously worked with Acuitas, was using its own lipid nanoparticle to the same end. Despite having played such a key role in the story, Dr. Cullis said he was still stunned a year ago when trial results showed mRNA vaccines had an efficacy of about 95 per cent.

“That was really incredible,” said Dr. Cullis, who describes himself as a scientific entrepreneur. “I mean, you do what you do, and then something like this happens. It’s just amazing.”

He added that vaccines only scratch the surface when it comes to potential applications for the made-in-Canada lipid nanoparticle technology. Another direction Acuitas is pursuing in partnership with Verve Therapeutics, a U.S. company, is a gene-editing drug that can lower levels of bad cholesterol to help prevent cardiovascular disease.

Both the university and federal programs supported the work at key points, Dr. Cullis said. And a key to its success was holding on to the critical mass of expertise that built up around the effort.

“It’s vital to keep people local … and I think we should be doing more to retain our talent in Canada,” he said. “Countries that invest in their human capital are always going to do better.”

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