Canadian Miron’s DNA binder is a breakthrough in cancer treatment

By Hermione Wilson

Twenty-eight–year-old Caitlin Miron’s discovery of a novel DNA binder that could represent a significant breakthrough in cancer treatment won her the Mitacs Award for Outstanding Innovation – PhD in 2017. The Queen’s University’s PhD student spoke to us about her work and where she will go from here.

Walk me through your discovery of the DNA binder.

What our lab is looking at is the recognition of this unusual DNA architecture with small molecule binders. You can think of it as a necklace. You’ve got a chain and you’ve got beads that are freely moving along that chain, and they move along that chain until they get to a knot. Once they get to that knot, they can’t get past it. Now, you could go in and untangle that knot, but somebody else has gotten there first and they’ve superglued it together. Basically what that amounts to, is that chain is a temporarily single-stranded DNA and the beads moving along it are your enzymes that are processing that DNA, and the knot is your quadruplex. What we’ve discovered is essentially a superglue that’s going to stabilize that quadruplex and prevent the cell machinery from accessing what comes after it. Based on our results, we’re seeing that it’s probably one of the best stabilizers in the field to date.

Are there others out there?

There are others out there. It’s a relatively young field; it’s maybe 20 or 30 years old. The collaborator we actually made the discovery with (Jean-Louis Mergny, Research Director at the European Institute of Chemistry and Biology in Bordeaux, France) was somebody that had previously worked with my supervisor on a different quadruplex ligan.

You were at the European Institute of Chemistry and Biology when you made your discovery, correct? Why were you there?

I’ve spent two summers there essentially – a three-month internship and a four-month internship. The first year when I went over I had an NSERC (Natural Sciences and Engineering Research Council of Canada) grant, we thought we would apply for the travel supplement that you can get with it, and we had a little bit of a pre-existing collaboration there so we thought, why not? As a lab we have been interested in DNA recognition, but we weren’t specifically, at that point, entrusted in guanine quadruplexes. But when we discovered that really amazingly stabilizing compound, it kind of changed our focus.

What are the implications of this discovery for cancer therapy?

We’re still very much in the fundamental research stage of analyzing these things and developing them further, but we do have very preliminary results from a cancer cell line screening that show that we have certain human cancer cell lines where we do see an inhibition of cell growth in the presence of our binders, so they may end up representing an alternative to more traditional chemotherapeutic agents that might potentially be slightly safer with less side effects. Aside from that, guanine quadruplexes have been implicated in other diseases as well. There’s at least one that is around the region of the protein responsible for infection by HIV, and there are genetic disorders as well. So there are a number of diseases, we’re just focusing on cancer first. We have more resources on it.

Now that you’ve returned to Canada and to Queen’s University, what are your plans to further the work?

Since coming back it’s been a little bit of a double strategy. I’ve been able to identify a number of techniques that were useful in Bordeaux that we can translate back to Queen’s and adapt into the instrumentation that we have here. At the same time, we’re also looking at the progress we’ve made so far and going, OK, where do we want to take these compounds and how do we modify them to perhaps target cancer cells better or improve entrance to the cell membrane, and those kinds of things. So I am back at the bench doing chemistry.

What is it about Queen’s University that makes an ideal place for you to do this work?

We have a very strong chemistry department so there is a lot of knowledge here, and it’s a very international department. We also have a lot of instrumentation. We’ve got great NMR (nuclear magnetic resonance) facilities; I have access to some very good fluorescent spectrometers and so forth, and we have the space to do the research that we need. We have the resources to work on the biochemistry side of things, but we also have the facilities we need to do all the chemistry that has to get done as well.

When you say it is a very international department, what do you mean?

I mean the faculty and the graduate student community. There is a strong international cohort, which is kind of nice because you end up with people who have different perspectives on the same problems and, as I learned in Bordeaux, that’s really valuable.

Have you had any contact with pharmaceutical companies or industry partners of any kind who are interested in your discovery?

Not at this point. We filed the provisional patent in November [2017]. We’ll probably end up having to file a second provisional patent. It won’t go public for a year, until a formal patent has been filed, and at this point it is a joint patent with our inventors here and the ones in Bordeaux: John-Louis [Mergny] and [Anne] Petitjean (Miron’s supervisor at Queen’s and head of the Petitjean Group) and me.  Queen’s will be ultimately responsible for identifying partners who might be appropriate for us to license this to. We’re not quite there yet; I think within the next two to five years we might see something happening that might be quite exciting, but we’ll see.

 What does it mean to you to win the Mitacs Awards for Outstanding Innovation – PhD?

It’s a really great honour. As a researcher, the best reward was actually the funding to go over and do the research, because at the end of the day, that’s what I do and that’s what I care about. I really love what I do and I want to be able to do it in the best way possible. But the Mitacs Award, it’s an acknowledgment that, a) the research is valuable, and that, b) I’m doing a good job with it. Also knowing it was my supervisors who nominated me, there’s a bit of recognition there as well. It’s pretty amazing.

 Does the award come with any monetary component?

I don’t think so, no, but I’ve done a bunch of media interviews, [and I joined] the Mitacs delegation to Parliament Hill, in [November 2017]; that’s kind of a lobbying effort. I think in terms of where I want to go in the future, it will be valuable for me.

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