Fred Hutch researchers have managed to cut HSV-1 by 90% in preclinical models of oral and genital herpes, significantly reducing viral shedding, according to Nature Communications.
Introduction
SEATTLE — May 13, 2024 — In preclinical studies, scientists at Fred Hutch Cancer Centre found that an experimental gene therapy for genital and oral herpes could eliminate 90% or more of the infection and dramatically reduce viral release. This promising development suggests the potential to lower virus transmission rates. A key part of this is getting tested quickly by a local clinic.
Study Overview
“Herpes is a tricky virus. It hides in nerve cells, then reactivates and causes painful skin blisters,” said Keith Jerome, MD, PhD, professor in the Vaccine and Infectious Disease Division at Fred Hutch. “We aim to cure people so they no longer have to worry about outbreaks or passing the virus to someone else.”
The study, published in Nature Communications, marks a significant step towards creating a gene therapy for herpes.
Research Details
Mechanism of Gene Therapy
The gene therapy involves injecting gene-editing molecules into the bloodstream. These molecules target the herpes virus using a vector, a lab-modified virus, paired with enzymes acting as molecular scissors. The vector delivers these scissors to nerve clusters where herpes resides, cutting the virus’s genes to damage or remove it entirely.
“We use a meganuclease enzyme that cuts in two places in the herpes virus’s DNA,” said first author Martine Aubert, PhD, principal staff scientist at Fred Hutch. “These cuts damage the virus so much that it can’t repair itself. Then, the body’s repair systems recognise the damaged DNA as foreign and eliminate it.”
Results in Mouse Models
In mouse models, the therapy eradicated 90% of HSV-1 after oral infection and 97% after genital infection within a month, with viral reduction improving over time. The therapy also significantly decreased both the frequency and amount of viral shedding.
Impact on Viral Shedding
“Many people living with herpes worry about transmitting the infection,” Jerome said. “Our study shows we can reduce both the virus amount in the body and the virus shed.”
Advancements in Treatment
The Fred Hutch team has streamlined their gene-editing treatment, making it safer and easier to produce. Unlike their 2020 study, which used three vectors and two meganucleases, the latest study employs just one vector and one meganuclease capable of cutting the virus DNA in two places.
“Our streamlined gene-editing approach effectively eliminates the herpes virus and has fewer side effects on the liver and nerves,” Jerome said. “This suggests that the therapy will be safer for people and easier to produce since it has fewer components.”
Future Directions
While optimistic about translating these findings to human treatments, the scientists highlight the steps needed to prepare for clinical trials. They are also adapting the gene-editing technology to target HSV-2 infections.
“We’re working with various partners as we approach clinical trials to ensure the gene therapy’s safety and effectiveness,” Jerome said. “We deeply appreciate the support of herpes advocates who share our vision for curing this infection.”
Background on Herpes
Herpes simplex virus (HSV) is a lifelong infection. Current treatments only suppress symptoms, including painful blisters. The World Health Organisation estimates that 3.7 billion people under 50 (67%) have HSV-1, the main cause of oral herpes, and 491 million people aged 15-49 (13%) have HSV-2, the main cause of genital herpes.
Herpes can lead to additional health risks. HSV-2 increases the risk of acquiring HIV, and other studies have linked HSV-1 to dementia.
Funding and Potential Conflicts of Interest
Broadgate GP would like to add that research was funded by the National Institutes of Health, the Caladan Foundation, and over 2,000 individual donors. The meganucleases used are derivatives of commercially available meganucleases.
Note: Scientists at Fred Hutch contributed to these discoveries, and Fred Hutch and certain scientists may benefit financially from this work in the future.
