October 08, 2021

mRNA – the talk of the town

By Conor McKechnie and Dodi Axelson

mRNA – the talk of the town

Who (in the scientific community) would have guessed that mRNA would be such a popular word in everyone's vocabulary one day? Well, as Conor puts it, "all the research by the people on the edges of the scientific community for the past 20 years are really paying dividends."

Join Dodi, Conor and their guests, Clive Glover the General Manager of Gene Therapy at Pall and James Taylor General Manager in Vancouver for Precision NanoSystems, in the latest episode of Discovery Matters, talking about mRNA revolutionizing the genomics field.

DODI: Conor hit me with everything you know about mRNA. Go!

CONOR: Well, it's a very little amount apart from everything that everyone has been talking about for the last year. So, in its most basic form, messenger RNA is a single stranded molecule of RNA that corresponds to the genetic sequence in a gene, and it's held together by a ribosome. Am I close, in the process of synthesizing proteins?

DODI: Spot on! Thank you, you saved everybody looking it up in Wikipedia™. Like you said earlier, this has become the talk of the town since two of the COVID-19 vaccines are based on that technology.

CONOR: That's right. And now all the research by these people on the edges of the scientific community for the past 20 years are really paying dividends.

DODI: That's right, and mRNA is revolutionizing the genomic field. Have a listen to this!

CLIVE GLOVER: The diversity of diseases that genomic medicine can be used to treat means it's really this toolbox. And you can look at what is the underlying genetic cause of the disease. And you can go into your toolbox and find the appropriate tool to then fix that. Scientists can continue to use their creativity and imagination to dream up more ways of doing it. So, it's really just this great toolbox that gives you a whole bunch of different degrees of freedom as to how to solve these problems. And that's why I think it's going to have a long-lasting effect on the way we treat disease.

CONOR: And who's this?

DODI: This is Clive Glover, he is the General Manager of Gene Therapy at our sister company, Pall.

CONOR: Ah, Clive, yes!

CLIVE GLOVER: I've always been fascinated by biology and the more physical sciences and how they came together. I started off my undergraduate career, actually, with a degree in physics, and pretty quickly realized that I found that subject in and of itself quite dry. And so, I was forced against my will, in university, to take a biology course in first year and actually suddenly realized that it was something I really enjoyed. And I managed to bring the two subjects together in my undergraduate studies and then later on in my graduate studies. I've always sort of kept going on that. And that's taken me through a really great journey in this advanced therapy space that is becoming so so relevant today. As these new areas open up, and particularly in the therapeutic space, which is where I'm very focused now, I've become very interested in learning about more of these areas as they evolve and develop and just seeing what are the new things that they're able to tackle, particularly in the case of human disease.

DODI: And Clive is joined by James Taylor, who is the General Manager in Vancouver for Precision NanoSystems, also part of our family of Life Sciences companies within Danaher, and James always knew he would become a scientist.

JAMES TAYLOR: Because in training, as an undergraduate, I did engineering, physics, and then PhD in genetics, and really had a focus on my career around engineering, biology, and entrepreneurship. I suppose when I was younger, I aspired more towards the physicists and that field, and hence going into the physics degrees early on, but then wanted to make a big impact in health. So, then augmented the education with the genetics PhD, and really overarching as a strong believer of technologies and the impact and the need for new technologies to solve key challenges in society. And so, I think in the fields that we are involved in, particularly in these areas of high unmet medical need, new technologies are required to really make a big impact.

CONOR: So, what exactly are they doing in their work related to mRNA?

DODI: Well, our bodies are encoded and regulated by our own genetic material consisting of RNA, DNA and proteins. So, people like James and Clive are working on enabling genetic medicines to deliver RNA and DNA into cells to affect that genetic regulation. Essentially, aiming to fix disease and promote healing on the same playing field as our own biology.

CONOR: Okay, so that's absolutely fascinating. I can see it being the future of medicine and I can totally understand why Clive and James are so interested in the potential here.

DODI: Incredibly, they both see mRNA as the genetic toolbox to solve a vast quantity of problems for medicines and vaccines.

CONOR: So, I like that idea of 'genetic toolbox'. It's a little bit like Bob the Builder™, but with much smaller, much cleverer tools.

DODI: 'Can we fix it? Yes, we can.' And these genetic tools can be amended to fix medicines.

CONOR: So, you talked about the COVID vaccines that use mRNA technology. The other approved vaccines are based on viral vector technology. So how did one lead to the other?

DODI: We're going to find all that out on this episode of Discovery Matters. So, to learn how the viral vector technology eventually led to working with mRNA technology, we actually have to learn a bit more about the friendship between Clive Glover and James Taylor. These two went to university together. But it was only when they bumped into each other at a conference only a couple years ago, that they started to talk about alternatives to viral vectors.

CONOR: A small world, heh? Amazing.

CLIVE GLOVER: I was very focused on the viral vector field and starting to think about alternatives to viral vectors for the delivery of genetic information to the body. And I think that's how we started getting to talk, and lipid nanoparticles came up as an obvious alternative to viral vectors. We started talking and then started talking with others at Danaher, and Pall ended up actually, you know, making an investment into Precision NanoSystems. I joined the Board of Directors for a couple of years, and then Pall acquired Precision NanoSystems in May of 2021. So, I think it just shows, you know, the value of personal relationships in some of these things.

CONOR: So, this is a natural, even kind of, predestined development Dodi, or was it just like chance?

DODI: Well, Conor, Clive and James and I talked about that very thing.

CLIVE GLOVER: Destiny, yes, it was highly likely that RNA based therapeutics and genomic medicines would come to market in some time frame. But I think the revolutionary part of it was the fact that we've had a huge disrupter in the form of COVID-19 pandemic, which has meant that the mRNA medicines in particular have come to market much, much quicker than they maybe would have done without that stimulus. I think it really took that dramatic event to really bring them to the forefront much quicker than they would have done otherwise.

JAMES TAYLOR: I think we're seeing a similar dramatic revolution happening here. And so, we're able to really do things faster, progress the field faster, and accelerate that than anything we've seen before in medicine. So, I think the future is extremely bright for this field. And we'll see tremendous innovation, both in how we can treat disease, but also how medicine is distributed and administered.

CLIVE GLOVER: Yeah, and the part that I would add is to say that, you know, anytime you get a new kind of technology, it can seem scary to some people. And we've certainly seen that with the uptake of a lot of the vaccines. And sometimes these genomic medicines can sound like scary things as well. But what I'd say is that, particularly with mRNA therapies, we've had the most fantastic proof of safety with the success of the COVID-19 vaccines. Never before has a technology been tried out on such large numbers of people and shown to be safe and effective as we've seen on these mRNA therapies. And so, I think that's just a tremendous sign of the value of these kinds of technologies.

DODI: Clearly, mRNA has huge potential, as we've all seen during this pandemic.

JAMES TAYLOR : If you have a rare disease that's caused by a mutation in one of your genes, that causes the protein that it encodes to no longer work, putting that back and enabling that patient by delivering say RNA to express a functional protein can have a very strong effect. And then this past year, what we've seen with RNA vaccines and COVID, what we're doing there is we're again expressing or encoding signatures of the bug that we can then use and deliver to the body to express to teach the immune system of that given pathogen. So, when we actually see it in the wild, our immune system is primed to get rid of it.

CLIVE GLOVER: Yeah, so what I find fascinating is the fact that everybody can now name who made the COVID-19 vaccine! I mean, for us in the business, the Modernas and the BioNTechs and Pfizers, of course, you know they're routine names for us. But for just the average person in your street, that's not engaged in the pharmaceutical industry, these are not regular household names. So, I find it fascinating. And I'm hoping it's now coming down to where it's not just the name of the company, but also the kind of technology that's being used to actually make these vaccines. I must say that despite the fact that I've been involved in the advanced therapeutic field for more than 20 years, I think the number of ways that these genomic technologies are able to influence and cure in many cases, human disease continues to surprise me. Just looking at the creativity of scientists out there and the way that they use these tools to solve these diseases is quite fascinating.

CONOR: So, it can be used for vaccines, and to help our bodies to heal themselves. So, surely for genomic medicines... Is it just full steam ahead, everyone on the mRNA train?

DODI: It can seem like it if you read the headlines, but there are some short-term issues. And there's a whole lot of work going on in the background.

CLIVE GLOVER: I think the short-term thing that is holding us back is really just the people with the know-how, as I say, though, I think that is a relatively short-term problem, because this should be a substantially easier field to get into compared to other areas. So, I think it's just people at the moment to really do this sort of stuff. But that'll get solved soon.

JAMES TAYLOR:The barrier is going to be the clinical validation of the different modalities, and unlocking through delivery, being able to deliver these genetic medicines to different tissues. So those are the key things, once you can deliver an RNA to a liver, it would be a good example, you can access all of those disease targets that are in the liver. And so very rapidly, you're seeing drug companies develop therapeutics against all the main targets that could be there. I think also, as we go from the genesis on this field, and targeting diseases that have very well-defined disease etiology and genetic etiology to more complex diseases, that'll take some time and an understanding of the biology as well. But things can happen really quick once the technology has been validated and demonstrated.

CONOR: Okay, this is interesting. So, the issues, you know, far from being technical alone, there's just not enough people with the know-how for the time being, and there's a potential cost barrier. But with time that should become less of a problem as they do in many industries with new technologies, right?

DODI: Completely. And James was particularly hopeful and confident that the future of mRNA really has no limit.

JAMES TAYLOR: I would say we've heard a lot of news this year, this past year and a half to two years now on mRNA technologies. But the genetic medicine toolbox is much bigger than that. There are all sorts of different tools that we can use to treat disease. And these technologies are being applied to solve areas of high unmet medical need in infectious disease including cancer, rare diseases, metabolic diseases, really every type of indication. So, it really is an exciting time in biotech, and tremendous innovation is happening very quickly and accelerating, meaning that as citizens and patients, we're going to have more tools to help treat our diseases as they come.

DODI: This tremendous innovation is really exciting as genetic medicines, that are based off of mRNA technology, are showing that this is likely to become the common way of treating disease. And of course, I'm sure it didn't escape your attention Conor the recent headlines, saying that Moderna is now testing its mRNA technology on trials for an HIV vaccine.

NEWS JOURNALIST: With COVID cases dropping, mRNA technology is setting its sights on a new complex target. Moderna is taking aim at human immunodeficiency virus or HIV.

CONOR: Exactly. Yeah. So, there's a whole series of different applications that are suddenly being taken seriously given that we now have proof that it works in the wild, as it were.

DODI: That's right. It's like James says, no limit to the possibilities of the future in mRNA innovations.

JAMES TAYLOR: So, I believe that genetic medicines will become the most common technology and that every scientist can now be a drug developer through genetic medicine. So, yeah, really akin to the transition from analog to digital technologies, genetic medicines are enabling a similar disruptive translation, which we talked about a little bit earlier. But really, once you know, a disease, how you want to treat a disease, or what disease gene you want to target, and which way you want to do that, you can very rapidly now find the sequence of the molecule you want to use as the drug substance, and essentially print it out, go to a supplier or print it out on a machine. And so, this is just dropping the barrier for how people can develop drugs in ways that haven't been possible so far. And we're seeing that scientists who do not have drug development backgrounds are able to rapidly get into this field. And it's very exciting, you know, to unlock just so much innovation, and so much activity in therapeutics that hasn't existed before. It's extremely exciting.

CONOR: This is one of the reasons why I both love the industry that we work in Dodi and that it's also a kind of a constant frustration, right? Innovation and excitement. And then kind of the hurdles that you don't expect. We discover something new, we get really excited about it, and you get that kind of hype curve, and then you reach barriers that you may not have seen. So, I'm kind of interested in what might be the barriers that mRNA runs into that we haven't anticipated yet.

DODI: Yeah, we'll find those out for sure. But I think, you know, to be ever the optimist, I think in this industry, there's always a friend that's going to push the boundaries with you or push through those limitations. Friends like James and Clive, you know, meet up somewhere, have that conversation, keep that curious door open, and then boom, you find the way forward to the next innovation.

CONOR: That's so real, isn't it? It's so true. It's like as much as it's about the science and the technology, the fundamental piece that makes this industry just so cool to work in is the people, the lovely, wonderful human beings we work with.

DODI: And on that note, we say thank you for listening to this very optimistic episode of Discovery Matters.

CONOR: And Discovery Matters' executive producer is Andrea Kilin and was produced with the help of Bethany Grace Armitt-Brewster. Music by Thomas Henley. And finally, thank you to Clive and James. My name is Conor McKechnie.

DODI: My name is Dodi Axelson. And hey, can you do us a favor please, and give us a rating on the platform that you listen to us on because we're just wondering if you're out there?

CONOR: Do you even you exist?

DODI: Bye for now.

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