CRISPR gene editing to remove HIV infection

Researchers presented some preliminary data at a conference in Spain this week showing that they have successfully used the Nobel prizewinning gene editing tool “Crispr” to eliminate human immunodeficiency virus - or HIV, from infected cells in culture. HIV is problematic to cure because it inserts covert copies of its genetic code into our human DNA. It’s from these “hidden” viruses - that lurk off the immune radar - that HIV stages a comeback whenever infected patients stop taking medication. So editing them out successfully is a step closer to ridding the body of the infection, as the BBC’s digital health editor, Michelle Roberts, explains…

Michelle - They've used this technology that has been around for a few years now. It won a Nobel Prize back in 2020. And if you look at cells on the molecular level, it's like a little pair of scissors that can snip out bits of DNA, it's called gene editing. CRISPR is the actual technology we're talking about. Those little scissors can go in and start changing things within the cell and hopefully that could be really helpful because with HIV, we know that this virus gets into cells, it hijacks them and starts using the cell's own machinery to make more copies of the virus. At the moment, we've got really powerful HIV drugs that people can take that can keep it at bay, but it can't get rid of it entirely. So there's still some HIV within the body.

Chris - And the argument is if you've got a mechanism for gene editing, you could go into the cells that are harbouring that genetic message and disable the genetic message, thereby disabling the infection.

Michelle - Exactly. So you either entirely snip out a bit of the HIV genetic code, the blueprint, or you just disable it so it can't do it very well anymore. They're saying that this is very early work, so at the moment they've been looking at cells in the lab, but another company has actually started trying to do it in a few people as well. But you also need to look at safety and whether it will work well enough because we've already got really good treatments for HIV.

Chris - Indeed because about 20 years ago, if you'd come up with this, people would've said, let's give it a go. I've got nothing to lose. But now we have a situation where a person with HIV adequately treated has got the same life expectancy as someone without HIV. So you're sort of saying to someone who's healthy that they have a potentially risky procedure, which might not be attractive to them.

Michelle - Yeah, it's still unchartered waters. I mean, people have been using this CRISPR, these little molecular scissors if you like, for other things too, because you can see how, if you can tinker with, with DNA and correct some things that are going wrong, you could treat lots of different things. They have been using it for some types of site loss, genetic site loss. They've looked at it for sickle cell disease, various things. And there are some early promising findings. But then also researchers are really monitoring what are the side effects because you might get some slight off target editing and that could cause other issues that might not be apparent at the moment.

Chris - What do we think the risk of that happening is? If it's good enough to go into people already? Presumably scientists think they've got a pretty good handle on how good and how accurate this set of molecular scissors can be made to be. So how risky is it?

Michelle - It's really difficult at the moment to put a number or if you had a patient in front of you, it would be really hard to say, well, one in 10 people have no side effects or, you know, some sort of tangible risk. The other difficulty with this type of technology is we're talking about such minute levels that you've got to get this way of editing into the cell and they found that this CRISPR technology, the packaging you need to get it into the cell is quite bulky. So these researchers at the moment who've been looking at HIV, have been trying to find different methods of getting that size of the package down small and small and smaller to get it into the cell efficiently.

Chris - And what about other viruses beyond just HIV? Because I think I read a few years ago, people were saying when you catch one of the herpes viruses like chicken pox and get shingles because it keeps coming back or herpes simplex that causes cold sores because it keeps coming back from your nervous system. If we could do this sort of gene editing, you could disable that virus wherever it's resident in the body and then you wouldn't suffer painful blisters periodically.

Michelle - I mean that would make sense, there are lots of different infections that can lay dormant for a while but can then reemerge and cause problems. It would make sense if you can find the right genetic code, you can deliver this package that can get into the cell and start changing that DNA or disabling some of it without causing any side effects. That's the massive question mark here. You know, we need to be sure that these treatments are safe enough because even with chicken pox and other things that can reactivate, we do have other treatments out there.

Chris - And when you spoke to the team, were they confident they're going to be able to crack this nut or are they saying, look, this is promising but it's so far off into the future, don't hold your breath.

Michelle - They're very excited, but it's certainly not going to be tomorrow. And they were quite open about that. They were saying, you know, we really don't want to suggest that we've got a cure round the corner. It's not that, but it is exciting science and given that lots of people are exploring different diseases with this CRISPR technology, it's definitely one to keep watching and pushing on.