Almost all of us carry one form or another of the herpes virus, and the consequences can be far worse than the occasional cold sore. Herpes viruses also cause shingles and can be implicated in blindness, birth defects and even cancer – and as yet, we can’t rid ourselves of them.
One of our best ways to combat herpes viruses is by blocking the enzyme they need to copy their DNA so that they can replicate. But although this can keep the level of virus in your body down, it cannot wipe out the infection. Worse, it doesn’t work on dormant herpes viruses that are waiting inside our cells for the right time to flare up again.
But gene editing may allow us to destroy these latent viruses. Robert Jan Lebbink at the University Medical Center Utrecht, the Netherlands, and his colleagues are developing a therapy that might safely clear certain herpes viruses from the body by messing with their DNA.
Lebbink’s team have been experimenting with CRISPR, the gene-editing technique that can be used to cut DNA at precise points in a sequence. When carried out on DNA inside an organism or virus, the DNA snip is usually repaired, but this process often introduces mutations or errors at this cut site.
This means gene editing can help destroy dormant viruses. When CRISPR is used to cut viral DNA in two or more important places, there is a good chance that the DNA will not be repaired properly, leaving the virus unable to function.
Curing cells
When they tried this technique on a monkey or human cells infected with Epstein-Barr virus (EBV, pictured above) – a herpes virus that causes glandular fever and is associated with a range of cancers – they found that cutting the DNA in one spot reduced viral activity by about 50 percent, while cutting it in two places led to 95 percent of dormant viruses being lost from the cells.
“We could efficiently remove the latent genome from infected cells, essentially curing cells of their invader,” says Lebbink.
What’s more, the therapy seemed to have little effect on human cells hosting the virus – an important consideration when it comes to clearing herpes viruses from organs such as the brain.
Latent HSV-1 – a herpes virus most commonly associated with cold sores – proved more resistant to CRISPR tampering, although targeting two points in its genome did prevent the active virus from replicating. Lebbink speculates that the DNA in the dormant virus may be tightly compressed during latency, making it more difficult for CRISPR tools to access and cut it while it is dormant.
“Targeting the latent genome is absolutely a major aim,” says Rob White at Imperial College London. Previous work had already suggested that CRISPR could fight dormant herpes viruses, he says.
But there are significant challenges ahead before CRISPR can become an effective therapy. Not least is the problem of delivering the CRISPR machinery to infected cells.
“Delivery and safety are key issues that need to be solved,” says Lebbink – although progress is being made, he adds.
References:
Colin Barras (June 30, 2016). Gene editing could destroy herpes viruses living inside you [Blog post]. Retrieved from https://buff.ly/39cGLNo
