Editing out herpes
Nearly two thirds of us are infected with the herpes simplex virus, which causes cold sores, genital herpes and occasionally even brain infections. The virus is a headache to treat because the infection is lifelong. This is because the virus hides, existing just as a piece of DNA, inside nerve cells. It periodically re-awakens to produce painful, infectious skin blisters. And although there are drugs that can control these flare ups when they happen, they can’t remove the viral DNA, so the problem keeps recurring. Now, researchers in the US have developed a pair of selective molecular scissors that can track down the rogue viral DNA inside nerve cells and cut it up, destroying the virus so - at least in experimental mice - it can’t come back. Chris Smith spoke to Keith Jerome...
Keith - Herpes is really sneaky, in that it actually establishes a form of itself that essentially goes into cells and then falls asleep. And that virus lives in the neurons, the nerve cells in your body. And then it can come back once a year, once a month, once a week, and cause lesions and ulcers and anything else, and all those drugs we have don't do anything about that sleeping form of the virus.
Chris - So it's effectively under the immune radar then? All the time it's dormant inside cells like that, the immune system can't see it. So it just gets ignored.
Keith - That's exactly right. The immune system controls it once it wakes up and starts making more copies of itself, and they take care of those new copies, but even the immune system doesn't do anything about that long-term sleeping form of the virus.
Chris - So what can you do about it?
Keith - Well, we've been using this really cool technology, that's been around for a little over a decade now called gene editing. This virus is made of DNA just like our body is. And that sleeping form is a little tiny circle of this DNA that lives in the nerve cells. And what gene editing allows us to do is basically use what I think of as molecular scissors, that can go into a cell and they can look through all the DNA in that cell and look for a very specific little stretch of the letters. And if they find those letters, they make a little cut. And so what we do is design very special scissors that ignore all of our own DNA, all the human DNA, but they look really hard for herpes. And if they find it, they make two little cuts, and so it basically falls apart and makes it go away.
Chris - And this works does it? You can actually demonstrate that you chop up the virus, and it then can no longer come back?
Keith - Yeah, exactly. So the study that we did was in mice. Mice get this sleeping form of herpes, just like we do. And then we can go in and we use something we call a vector. It's a different virus that carries these scissors to those same neurons. And when it does that, it starts cutting up the virus. And then we can measure after our therapy, how much of that sleeping form is actually left in the mice, after we've treated. And what we saw is we eliminated well over 90% of that virus. And if we could translate that into human beings, it's likely to prevent lesions, and ulcers, and disease, and transmission to other people, and all the things that we worry about.
Chris - How did you get the virus that was the Trojan horse that carried in the molecular scissors? How did you get that into the nerve cells in these animals?
Keith - Well, that was a really important part of our study, understanding the best way to get the scissors where they need to be. And we use another virus, it's called adeno-associated virus. We actually almost all have it, never causes any disease. We basically changed that to carry these scissors for us. It's just injected into the bloodstream. And once it's in the blood, it actually goes in and finds those nerve cells and introduces the scissors.
Chris - It sounds like the woman who swallowed a fly, and then swallows a spider to eat the fly. And we all know how that story ends. Because you're basically giving someone a virus to treat a virus. Is this safe?
Keith - This particular virus vector that we've used, called adeno-associated virus, is probably the leading vector that's being used for many, many types of gene therapy now. And there's several approved products out there, in the EU, and in the United States that use, adeno-associated virus, or AAV, to deliver different types of gene therapy. And so we're taking something that's quite proven to be safe, modifying it slightly for our needs, and then using it to try to cure an infection where we've simply not had any hope for a cure in the past.
Chris - You've been looking at herpes simplex virus, this causes cold sores, and it also causes genital disease. But this is one member of a big family of viruses that all work in a similar sort of way. Things like VZV, the virus that causes chicken pox, and then shingles in people unlucky enough to have that. Do you think you could prevent a person from succumbing to shingles by the same technique?
Keith - The shingles virus goes into very similar nerve cells and acts a lot like herpes simplex. And so we can actually think about using the same therapy for that virus as well. We're also very actively looking at viruses that are similar, but not herpes viruses, in particular hepatitis B. And we have some really exciting results there where we can do very similar things. We're likely to see success there and maybe in other viruses as well.