Quirks & Quarks·Q&A

Meet the Canadian scientist who paved the way for groundbreaking mRNA COVID vaccines

Pieter Cullis developed an essential technology for the most successful COVID vaccines — the packaging that protects the delicate vaccine payload and delivers it to our cells.

UBC researcher developed the packaging for the vaccine's payload that delivers it to our cells

Pieter Cullis is a professor of Biochemistry and Molecular Biology at the University of British Colombia. He developed an essential technology for the most successful COVID vaccines. (Paul Joseph/UBC)

Every week, more Canadians are rolling up their sleeves to get the shot that will protect them against COVID-19. 

One of the breakout vaccine technologies of this pandemic are the mRNA vaccines developed by Pfizer-BioNtech and Moderna. Those were some of the earliest vaccines out of the gate because of how easy they are to create. They also work incredibly well.

Delivering these vaccines into our bodies would not have been possible without the work of Pieter Cullis, a professor of biochemistry and molecular biology at the University of British Columbia.

Quirks & Quarks host Bob McDonald spoke with Prof. Cullis about his technology. Here is part of their conversation.

What is the technology you created that's been essential to RNA vaccines? 

The RNA vaccines have a fundamental problem that requires a delivery system to enable the messenger RNA, the mRNA, to get into cells. What we've been working on is our so-called lipid nanoparticles that encase the RNA and protect it from degradation, but also enable the mRNA to be taken up into a cell and to be released into the cytoplasm — that's the inside of a cell — where it can actually be translated to form any protein you want. In case of vaccines, it's a protein that corresponds to one of the proteins associated with the virus. 

What are they made of? 

They're made of fats, your body has a lot of fat and not just the normal kinds of fats one normally thinks of. These are lipids that constitute the membrane that goes around all the cells in your body. You have a few trillion cells in your body, and all of them have a membrane around the outside. We use the same lipids in some cases as are present in those cell membranes, with a couple of extra additions. 

To see something that was 95 percent effective in preventing infection was really startling.- Dr. Pieter Cullis, University of British Columbia

You can think of them as little little balls of fat if you want to take a simplistic view. And they're really small. We're talking about systems on the order of 60 to 100 nanometers in size. And just to give you a bit of that scale, about one one hundredth the size of, say, a normal cell in your body. So this size range allows them to be taken up into the cell quite efficiently. 

You've been working on this for 40 years now. What did you first develop these lipid nanoparticles for? 

My interest is in trying to figure out the roles of all these typical biological membranes, that might have a thousand different lipids in it. And so my research was originally focused on trying to understand why they're all there and what their particular roles are. So we made simple model membrane systems, as they're termed, that consist of, say, one species of lipid, and then you can start to investigate what their properties were. We found that we could load cancer drugs into these systems. This led us to embark on a much more applied direction where we were trying to get the cancer drugs more specifically to a tumour, for example. 

Allison Downing, a registered nurse, prepares the Pfizer-BioNtech COVID-19 vaccine at a vaccination clinic in Dartmouth, N.S. (Andrew Vaughan/The Canadian Press)

But then in about the mid-90s, we said, OK, let's tackle some bigger molecules. So over the last 25 years, we've been trying to develop systems that will get these much larger entities, such as messenger RNA into target cells, and those efforts culminated with the Pfizer-BioNtech COVID-19 vaccine. 

It's an amazing evolution to go from delivering cancer drugs to delivering messenger RNA. How is the RNA different? 

The major thing, of course, is that it's much bigger. Most of the so-called small molecule drugs that we use, everything from aspirin to cancer drugs, are really small molecules. And the reason that we use these small molecules is because they're the only molecules that can get inside cells to really affect a process going on inside a cell with larger molecules. 

Prof. Pieter Cullis created lipid nanoparticles (illustration and image on the right) that can deliver a mRNA genetic payload. For the COVID-19 mRNA vaccines, the mRNA inside the lipid nanoparticles code for the SARS-CoV-2 spike protein, so once it's delivered and manufactured inside your cells, your immune system will learn to recognize it. (Pieter Cullis/UBC)

RNA and DNA, one major problem is how do you get those inside a cell? This was a major part of the evolution over the last 25 years. First of all, trying to develop systems that would encapsulate those big molecules and then secondly, trying to find ways to enable them to get to a target cell and then to deliver the RNA inside that target cell. 

What went through your mind when you realized how well the Pfizer-BioNtech vaccine worked against the coronavirus? 

In the past, you know, in terms of whether or not the FDA would approve a vaccine, was around about 50, 60 percent efficient. In other words, in 60 percent of recipients, it would prevent them from contracting the disease. To see something that was 95 percent effective in preventing infection was really startling. 

So you're using lipid nanoparticles to deliver the RNA instructions to the cells in our bodies, for making the tiny fragments of the virus, that the body then recognizes and alerts the immune system? 

That's correct. It's a really elegant approach. You're not putting the whole virus in. It's only a very small segment. There's no chance of viral transmission or anything like that. It's a vaccination technique that I think we're going to see coming in quite a variety of other applications, everything from influenza to HIV, cancer vaccines, etc. So it's a very powerful approach to vaccination. 

People receive mRNA COVID-19 vaccines at a mass vaccination facility in Brampton, Ontario. The technology that delivers mRNA into the body was made in part thanks to Canadian researcher Dr. Pieter Cullis. (Nathan Denette/The Canadian Press)

Do you think these lipid nanoparticles will be the new standard, that they'll replace the traditional way of delivering vaccines for viruses? 

They're certainly going to give viruses a good run for their money. You know, it's not just the fact that, you know, we're seeing these really potent immune responses. It's also that they're so adaptable. The turnaround time in terms of adapting to new pandemics is really very short, which is obviously a huge advantage. 

So it's a very, very exciting time and there's a real amazing sense of opportunity in the air at the moment. 


Q&A was edited for length and clarity. Produced by Sonya Buyting.

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