Fig. 8: Simplified meganuclease therapy decreases peripheral shedding in infected mice.

a Experimental timeline of ocular HSV-1 infection, meganuclease treatment and viral reactivations with JQ1. b Schematic of active m4 and inactive m4i meganuclease. c-d, HSV loads in both SCGs (c; p < 0.0001 for m4) and both TGs (d; p = 0.003 for m4) from control infected mice and infected mice treated the active m4 or inactive m4i (n = 10 per group). Percent decrease of HSV loads in treated mice compared to control mice and statistical analysis (unpaired one-tailed Mann-Whitney test with *p < 0.05; ****p < 0.0001; ns: not significant) are indicated. e–g Virus titers in eye swabs collected at day 1 to 3 after each JQ1 reactivation from control infected mice (e) and infected mice treated with active m4 (f) or inactive m4i (g). h, i Area under the curve (AUC) analysis of virus shedding after first (h), and second (i) JQ1 reactivation from control infected mice and infected mice treated with active m4 or inactive m4i (n = 10 per group). p values (unpaired one-tailed Mann–Whitney test) are indicated. j Inflammatory cell foci (ICF) in liver sections from either HSV-infected control mice, mice treated with active m4 or inactive m4i (n = 10 per group); p = 0.0234 for m4. k, l Severity scores of axonopathy (k; p = 0.0007 for m4) and inflammation (l) in TG from HSV-infected control mice, mice treated with active m4 or inactive m4i (n = 10 per group) with statistical analysis (Ordinary one-way Anova, multiple comparisons with ns: not significant; *p < 0.05; ***p < 0.001). Each graph shows individual and mean values with standard deviation. AAV viral loads are shown in Supplemental Fig. 9m–o. Source data are provided as a Source Data file.