New Gene Editing Approach Eliminates 90% of Latent Herpes Simplex Virus 1

Article

Researchers used 2 pairs of genetic scissors to remove latent herpes simplex virus 1, an approach they say should move toward clinical trials.

Investigators have used a new gene editing approach to remove latent herpes simplex virus 1 (HSV-1), finding at least a 90% decrease in the latent virus in animal models. The study authors said this is enough to keep the virus from returning.

According to the study, published in Nature Communications, most research on herpes focuses on suppressing painful symptoms rather than ways to cure the disease. The infection typically causes cold sores and is lifelong, affecting two-thirds of the global population under 50 years old.

“This is the first time that scientists have been able to go in and actually eliminate most of the herpes in a body,” said senior author Keith Jerome, MD, PhD, in a statement. “We are targeting the root cause of the infection: the infected cells where the virus lies dormant and are the seeds that give rise to repeat infections.”

The study used 2 sets of genetic scissors to damage the DNA of the virus, adjusted the delivery vehicle to the infected cells, and targeted the nerve pathways connecting the neck to the face. These pathways reach the tissue where the virus remains dormant in patients with the infection, according to the study authors.

The authors found that when using just 1 pair of genetic scissors, the virus DNA can be repaired in the infected cell. By combining 2 sets of gene-cutting proteins called meganucleases, however, they were able to cut an entire segment of herpes DNA, causing the virus to fall apart completely.

“We use a dual meganuclease that targets 2 sites on the virus DNA,” said first author Martine Aubert, PhD, in a press release. “When there are 2 cuts, the cells seem to say that the virus DNA is too damaged to be repaired and other molecular layers come in to remove it from the cell body.”

The genetic scissors are introduced into the target cells by delivering the gene coding for the proteins with a vector, a harmless deactivated virus that can enter the infected cells. After injecting the delivery vector into a mouse model, the investigators found a 92% reduction in the virus DNA present in the superior cervical ganglia, the nerve in which it lies dormant. The reductions remained for at least a month after the treatment.

According to a press release, the investigative team is also working on a similar strategy for herpes simplex 2, and 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 concluded. “I see it going into clinical trials in the near future.”

REFERENCE

New gene therapy approach eliminates at least 90% latent herpes simplex virus 1 [news release]. EurekAlert; August 18, 2020. https://www.eurekalert.org/pub_releases/2020-08/fhcr-ngt081420.php. Accessed August 18, 2020.

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