A recent article, published in Nature Communications, has revealed a gene editing approach that can eliminate levels of latent herpes simplex virus 1 (HSV-1).
Herpes simplex virus
HSV types 1 and 2 are widespread pathogens causing oral and genital ulcers, neonatal herpes and increasing risk of HIV acquisition in humans. After primary infection at the skin or mucosa, the virus establishes lifelong latency in the sensory and autonomic neurons of the peripheral nervous system. As a result, the virus is able to reactivate from this state, causing lesions and/or virus shedding at mucosal surfaces.
Current therapies can reduce the severity of acute infections and diminish viral reactivation frequency. However, these therapies do not reduce or eliminate the latent virus that continues to drive recurrent disease. Advancements in gene editing technologies, including CRISPR/Cas9 and meganucleases, offer the possibility of directly targeting these latent genomes for elimination.
Gene editing
Researchers at Fred Hutchinson Cancer Research Center used dual meganucleases to target multiple sites within the HSV genome. Specifically, the team used self-complementary adeno-associated virus vectors (scAVVs) to deliver the meganucleases into mouse models of HSV-1 infection.
First author and senior staff scientist at the Fred Hutchinson Cancer Research Center, Martine Aubert, stated:
“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 researchers found that meganuclease-mediated gene editing eliminated over 90% of latent virus present in the superior cervical ganglia. It also eliminated over 50% in the trigeminal ganglia.
The team believe these results provide support for continued development of gene editing as a strategy for latent HSV infections. They hope that if these observed levels were translated into humans, it would significantly reduce HSV reactivation, shedding and lesions. They suggest that with further optimisation of the delivery systems and meganculeases themselves, this approach is likely to offer a pathway to cure HSV infection.
Aubert continued:
“This is a curative approach for both oral and genital HSV infection. I see it going into clinical trials in the near future.”
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