In Vivo CRISPR Gene Editing in Patients with Herpes Stromal Keratitis
Wei, A.; Yin, D.; Zhai, Z.; Ling, S.; Le, H.; Tian, L.; Xu, J.; R Paludan, S.; Cai, Y.; Hong, J.
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In vivo CRISPR gene therapy holds large clinical potential, but the safety and efficacy remain largely unknown. Here, we injected a single dose of HSV-1-targeting CRISPR formulation in the cornea of three patients with severe refractory herpes stromal keratitis (HSK) during corneal transplantation. Our study is an investigated 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. One-Sentence SummaryOur study is the first in vivo CRISPR therapy for treating infectious disease and the first virus-like particle (VLP)-delivered gene therapy, reporting clinical follow-up to 21 months in HSK patients without seeing virus relapse, HSK recurrence, and CRISPR-associated side effects.
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