Developing CRISPR-Cas9 reagents for editing lytic and latent herpes simplex virus genomes

Herpes simplex virus (HSV) 1 and 2 cause significant morbidity and mortality, and HSV-2 infection increases the risk of HIV infection. Furthermore, HSV-1 infection is associated with increased risk of Alzheimer’s disease. HSV undergoes an acute lytic infection at the mucosal epithelium and spreads to establish a latent infection in sensory and central nervous system neurons for the life of the individual. Reactivation from latent infection is a major cause of herpetic disease. Drugs that target lytic infection are available, but drugs that target latent infection are not available. Thus, a therapeutic targeting HSV latent infection could reduce HSV latent infection and reactivation and the associated herpetic disease, Alzheimer’s disease, and AIDS.

We have identified a highly active CRISPR-Cas9 reagent that effectively edits lytic and latent HSV-1 genomes in cell culture. Therefore, we propose experiments to further refine the use of this approach for prophylactic and therapeutic treatment of acute and latent HSV infection in animal models. Commercial entities have expressed interest in latent HSV targets, and there is obviously a large market and demand for a “cure” for herpes as well as preventatives for AIDS and Alzheimer’s disease.