Researchers have successfully eliminated latent herpes simplex virus 1 (HSV-1) in mice using a new type of gene editing technique. While there is currently considerable research being conducted using the CRISPR-Cas9 gene editing tool, the researchers used a different, but highly efficient gene editing technique: AAV-delivered meganucleases. This approach was much more efficient at eliminating the virus, and allowed the researchers to eradicate 92% of latent virus from the superior cervical ganglia.
Herpes simplex virus (Types 1 & 2) are widespread, highly contagious, and cause oral and genital ulcers but also increase the risk of infection with HIV. The World Health Organization estimates that there are 3.7 billion people worldwide under the age of 50 who have oral herpes.
The virus establishes lifelong latency in sensory and autonomic neurons and can be periodically reactivated causing oral and genital lesions, with the viral shedding from mucosal surfaces. While there are antiviral therapies that can be provided to reduce the frequency and severity of outbreaks, there is currently no cure.
The researchers, led by Martine Aubert, PhD, of the Vaccine and Infectious Disease Division at Fred Hutchinson Cancer Research Center in Seattle, have been working on a cure using gene editing techniques to damage the DNA of the virus and render it unrepairable, thus preventing the latent virus from being reactivated.
The meganucleases were delivered using an AAV vector. Two proteins were used to make cuts to the DNA of HSV-1, as the virus was able to repair a single cut. The researchers were able to eliminate 92% of the virus using this technique which persisted for at least a month after treatment. The researchers believe the reduction would be sufficient to prevent reactivation of the virus, stopping further outbreaks.
The results were very promising, as if the level of reduction is translated to humans, the treatment would significantly reduce HSV reactivation, the formation of lesions, and viral shedding. The researchers also believe they can refine their technique to optimize delivery of the enzyme and meganucleases, and potentially decrease the level of virus in nerve tissue further still, and could potentially be a viable cure for herpes simplex infections in humans.
You can read more about the study in the paper – Gene editing and elimination of latent herpes simplex virus in vivo – which was recently published in the journal Nature Communications. DOI: 10.1038/s41467-020-17936-5