AAV-delivered gene editing for latent genital or orofacial herpes simplex virus infection reduces ganglionic viral load..., 2022, Aubert, et al

"Herpes simplex virus (HSV) establishes latency in ganglionic neurons of the peripheral nervous system, from which it can reactivate, causing recurrent disease and possible transmission to a new host. Current anti-HSV therapy does not eliminate latent HSV, and thus is only suppressive rather than curative. We developed a potentially curative approach to latent HSV infection and pathogenesis, based on gene editing using HSV-specific meganucleases delivered by adeno-associated virus (AAV) vectors. Our results demonstrated that a dual meganuclease therapy, composed of two anti-HSV-1 meganucleases delivered by a triple AAV serotype combination (AAV9, AAV-Dj/8, AAV-Rh10), can eliminate up to 97% of latent HSV DNA from ganglia in both ocular and vaginal mouse models of latent HSV infection. Using a novel pharmacological approach to reactivate latent HSV-1 in mice with the bromodomain inhibitor JQ-1, we demonstrated that this reduction in ganglionic viral load leads to a significant reduction of viral shedding from treated vs. control mice, with many treated mice showing no detectable virus shedding. In general, therapy was well tolerated, although dose-ranging studies showed hepatotoxicity at high AAV doses, consistent with previous observations in animals and humans. Also in agreement with previous literature, we observed subtle histological evidence of neuronal injury in some experimental mice, although none of the mice demonstrated observable neurological signs or deficits. These results reinforce the curative potential of gene editing for latent orofacial and genital HSV disease, and provide a framework for additional safety studies before human trials can begin."

doi: https://doi.org/10.1101/2022.09.23.509057

 

Mouse models. Extremely unlikely to be relevant to humans.

 

Isn't that were most interventions start though? Genuine question. I'm not understanding much of the text, but from glancing over it, it sounds like something you'd test a bit before actually trying it on humans.

 

No thanks. I'll wait until you have worked out how to avoid the liver and brain damage!

 

There are millions of animals used before drugs are tested on humans. I have researched and commented a lot on this, for example:

https://forums.phoenixrising.me/blo...her-slams-requirement-for-animal-models.1689/

Regrettably I'm not well enough to research further. But results in animals are really not worth reporting, as they very rarely translate to humans.