In vivo CRISPR gene editing in patients with herpetic stromal keratitis

In vivo CRISPR gene therapy holds large clinical potential, but the safety and efficacy remain largely unknown. Here, we injected a single dose of herpes simplex virus 1 (HSV-1)-targeting CRISPR formulation in the cornea of three patients with severe refractory herpetic stromal keratitis (HSK) during corneal transplantation. Our study is an investigator-initiated, open-label, single-arm, non-randomized interventional trial at a single center (NCT04560790). We found neither detectable CRISPR-induced off-target cleavages by GUIDE-seq nor systemic adverse events for 18 months on average in all three patients. The HSV-1 remained undetectable during the study. Our preliminary clinical results suggest that in vivo gene editing targeting the HSV-1 genome holds acceptable safety as a potential therapy for HSK. [Display omitted] Hong, Cai, and colleagues conducted the first in vivo CRISPR therapy for treating HSV-1 infection with the virus-like particle as the delivery vector, reporting clinical follow-up to 21 months as the longest and 18 months on average in three patients without seeing virus relapse, HSK recurrence, and treatment-associated side effects.