Simplified meganuclease therapy decreases peripheral shedding in infected mice. Credit: Martine Aubert
Researchers have discovered a potential gene therapy for genital and oral herpes that in pre-clinical trials removed 90% or more of the infection. Additionally, the gene therapy showed promise in suppressing the efficacy at which herpes is transferred between individuals, suggesting the treatment could help to reduce the spread of the virus.
"Herpes is very sneaky. It hides out among nerve cells and then reawakens and causes painful skin blisters," said Keith Jerome, professor in the Vaccine and Infectious Disease Division at Fred Hutch Cancer Center. "Our aim is to cure people of this infection, so that they don't have to live with the worry of outbreaks or of transmitting it to another person."
The research, published in Nature Communications, utilizes a mixture of gene editing molecules injected into a patient's blood to snip away at the virus's genes to damage them or even remove them entirely.
"We are using a meganuclease enzyme that cuts in two different places in the herpes virus's DNA," said Martine Aubert, principal staff scientist at Fred Hutch. "These cuts damage the virus so much that it can't repair itself. Then the body's own repair systems recognize the damaged DNA as foreign and get rid of it."
During trials using mouse models, the therapy eliminated 90% of herpes simplex virus 1 (HSV-1) after oral infection, and 97% of herpes HSV-1 after genital infection. Virus reduction took about a month to show these reductions, and evidence shows that virus reduction becomes more complete over time.
The team is currently working to optimize the method to include HSV-2 infections as they prepare for clinical trials. The researchers have also simplified the treatment, reducing it from three vectors and two meganucleases to one vector with one meganucleases, allowing for easier production of a safer gene editing treatment capable of cutting the viral DNA in two places.
"Our streamlined gene editing approach is effective at eliminating the herpes virus and has less side effects to the liver and nerves," added Jerome. "This suggests that the therapy will be safer for people and easier to make, since it has fewer ingredients."