Gene editing for HSV-1 shows significant reduction of viral load

Scientists at the Fred Hutch Cancer Center have discovered that an experimental gene therapy for genital and oral herpes removed 90 percent or more of the infection and suppressed how much virus can be released from an infected individual, suggesting that the therapy would also lessen the transmission of the virus.

Herpes simplex virus (HSV) is a common infection that lasts a lifetime once people are infected. According to the World Health Organization, an estimated 3.7 billion people under the age of 50 have HSV-1, which causes oral herpes and has been linked to dementia. An estimated 491 million people aged 15-49 globally have HSV-2, which causes genital herpes and increases the risk of acquiring HIV. At present, HSV therapies only suppress symptoms.

Dr Keith Jerome, professor in the Vaccine and Infectious Disease Division at Fred Hutch, stated: “Herpes is very sneaky. It hides out among nerve cells and then reawakens and causes painful skin blisters…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 experimental gene therapy involves injecting a mixture of gene editing molecules into the blood that find where the herpes virus resides in the body. The mixture includes a vector, as well as enzymes. When the vector reaches the clusters of nerves where the herpes virus resides, the enzymes cut the herpes virus’s genes to damage them or remove the virus completely.

First author Dr Martine Aubert, principal staff scientist at Fred Hutch, explained: “We are using a meganuclease enzyme that cuts in two different places in the herpes virus’s DNA…These cuts damage the virus so much that it can’t repair itself. Then the body’s own repair systems recognise the damaged DNA as foreign and get rid of it.”

In mouse models of the infection, the experimental therapy eliminated 90 percent of HSV-1 after facial infection and 97 percent of HSV-1 after genital infection. It took around a month for the treated mice to show these reductions, and over time, the reduction of virus appeared to become more complete.

Additionally, the team saw that the HSV-1 gene therapy had a significant reduction in both the frequency and amount of viral shedding. “If you talk to people living with herpes, many are worried about whether their infection will transmit to others,” Dr Jerome commented. “Our new study shows that we can reduce both the amount of virus within the body and how much virus is shed.”

Furthermore, the team’s gene editing treatment is safer and easier to manufacture, using just one vector and one meganuclease. Dr Jerome said: “Our streamlined gene editing approach is effective at eliminating the herpes virus and has less side effects to the liver and nerves…This suggests that the therapy will be safer for people and easier to make, since it has fewer ingredients.”

Although the team is hopeful about the gene therapy, considering its efficacy in animal models, they are careful about the steps required to prepare for clinical trials. “We’re collaborating with numerous partners as we approach clinical trials so we align with federal regulators to ensure safety and effectiveness of the gene therapy,” Dr Jerome concluded.

The team noted that they are working on adapting the gene editing technology to target HSV-2 infections as well. 

This study was published in Nature Communications.