Source: Fred Hutchinson Cancer Research Center 2022

Summary: Infectious disease researchers have used a gene editing approach to remove latent herpes simplex virus 1, or HSV-1, also known as oral herpes. In animal models, the findings show at least a 90 percent decrease in the latent virus, enough researchers expect that it will keep the infection from coming back.

Most research on herpes has focused on suppressing the recurrence of painful symptoms, and Jerome said that his team is taking a completely different approach by focusing on how to cure the disease.

How it works
In the study, the researchers used two types of genetic scissors to cut the DNA of the herpes virus. They found that when using just one pair of the scissors the virus DNA can be repaired in the infected cell. But by combining two scissors — two sets of gene-cutting proteins called meganucleases that zero in on and cut a segment of herpes DNA — the virus fell apart.

“We use a dual meganuclease that targets two sites on the virus DNA,” said first author Martine Aubert, a senior staff scientist at Fred Hutch. “When there are two cuts, the cells seem to say that the virus DNA is too damaged to be repaired and other molecular players come in to remove it from the cell body.”

The dual genetic scissors are introduced into the target cells by delivering the gene coding for the gene-cutting proteins with a vector, which is a harmless deactivated virus that can slip into infected cells. The researchers injected the delivery vector into a mouse model of HSV-1 infection, and it finds its way to the target cells after entering the nerve pathways.

The researchers found a 92% reduction in the virus DNA present in the superior cervical ganglia, the nerve tissue where the virus lies dormant. The reductions remained for at least a month after the treatment and is enough the researchers say to keep the virus from reactivating.

The team did other comparisons to fine-tune the gene editing approach:

– Gene cuts with meganucleases were more efficient that with CRISPR/Cas9.

– Refining the vector delivery mechanism, they found the adeno-associated virus (AAV) vector that was the most efficient at getting the gene edits to cells infected with the virus.The researchers are pursuing a similar strategy for herpes simplex 2, which causes genital herpes. They expect it to take at least 3 years to move toward clinical trials.

“This is a curative approach for both oral and genital HSV infection,” Aubert said. “I see it going into clinical trials in the near future.”