Interviewer: You never know where basic science will take you. Today, I'm talking to biochemist Wes Sundquist about a nature inspired system that can deliver molecules to human cells. We'll talk about that next on The Scope.
Announcer: Examining the latest research and telling you about the latest breakthroughs. The Science and Research Show is on The Scope.
Interviewer: Tell me what it is you've done here. You've made kind of a delivery system that can bring small molecules to other human cells. What is that?
Wes: Right. So what we've been able to do is to design new proteins that normally wouldn't have these activities to act like viruses in the sense that they can assemble into spherical particles. They can drive their own release from cells. And if we have the appropriate signals, they can enter new cells. Those are properties that we normally associate with viruses, but these are proteins that are designed in ovo and so we would envision that they can be more flexible in terms of what we can do with them than the nature viral systems.
Interviewer: Why is that interesting to maybe some of our listeners?
Wes: Right. So a couple of things, one is we've been for a long time interested in how viruses do this. So this is something that viruses are able to do, leave an infected cell and enter a new cell. That's how they spread infection, and we and others have been studying that those processes.
We wanted to know if we really understood them, and designing new proteins that normally don't have those properties but now acquire them is a good test of whether we understand the rules for how proteins assemble, how they bind to membranes, how they, what we call envelope themselves, that is wrap themselves in the membrane and how they bud, pinch the membrane off behind themselves. So this was a good test of whether we understood what's required for that process.
Interviewer: You know, viruses have a reason for wanting to spread themselves to other cells but why would you want to do that intentionally? Why would you want to deliver things to other cells intentionally?
Wes: So molecular genetics has over the last, perhaps five years, made great strides in terms of having the ability to do things like alter genomes with especially what's called the CRISPR/Cas9 system that can edit DNA so that it can correct, for example, genetic mistakes. The bottleneck now has become how do you deliver those very potent activities to new cells? So you could envision gene therapy situations in which you want to deliver potent enzymes that edit the genome and now you have to get them into cells. So that's really, as I said, a bottleneck and something that we and many other groups are working on trying to do efficiently.
Interviewer: And so, how did that feel when you actually saw that what you learned actually works, that you could tell a cell to do what you had thought it does?
Wes: I actually get excited all the time about research and when Jorg Votteler, who's the person who did the work and he deserves credit for that, came in and said, you know, it looks like it's working, and that was really the first time we tried it, which is an unusual situation in our lab. Usually, it doesn't work and then we sit there and try and figure out why not, but this was a case where the first design worked and that's partly a testament to Jorg, but it's also partly a testament to the fact that it just takes a lot of work to understand how things work, but once you do, you have opportunities to do things that you didn't before you understood how they worked.
Interviewer: That's right. I bet you never expected that your research on viruses would take you here.
Wes: Yes, that's right. There's a big field called nanoparticles and also a big field in terms of development of delivery systems, and we don't pretend to know all of it, but I'd follow it, but only from a distance and not envisioned that our lab was part of it, but I think that's the importance of research is that if you do it well, you don't know where you're going to end up, but I think you can be sure that as a field, things will move forward.
Interviewer: What else do you think viruses have to tell you? Or do you even know?
Wes: Yeah. So viruses have quite a history of teaching us really important things. So DNA replication was first reconstituted in mammalian DNA replication using viral systems. Of course, the discovery of the ACCA gene, so, cancer biologists don't often tell you this, but it wasn't cancer biologists, it was virologists who discovered that there were genes that when misregulated would cause cancer. And I think that there's just no doubt that they have more to teach us maybe particularly in the mechanistic area.
So we don't understand still how many of the machines work. They're exquisitely good at replicating things and moving around the cell, but also exquisitely good at reprogramming cellular pathways. So the great example is the ACCA gene but there are many other viruses modulate their environment. And then I think they're also teaching us a huge amount now about the immune system. So, I would say those are the three areas in which viruses continue to make a major conceptual contribution, not to mention, of course, the fact that they're important pathogens.
Announcer: Interesting. Informative. And all in the name of better health. This is The Scope Health Sciences Radio.
