Treatment for Herpetic Stromal Keratitis with CRISPR

Article: Local researchers develop cure for keratitis
Source: Shanghai Jiao Tong University (China) in Shanghai Daily, via Corneal Physician
Published: January 12, 2021
Article: HELP is on its way for herpetic stromal keratitis
Source: BioWorld
Published: January 19, 2021

Mouse eyes with different treatments

Herpes stromal keratitis (HSK) is a leading cause of infectious blindness worldwide. Yet, despite its high prevalence, there is as yet no vaccine for herpes simplex virus type 1 (HSV-1). After primary infection and replication in the cornea, HSV-1 is transported via ophthalmic nerves to the trigeminal ganglia (TG) where it can stay dormant and be reactivated in immunocompromised situations. With frequent recurrence and aggravation, the disease can lead to herpetic stromal keratitis (HSK) and potential blindness due to immune-mediated tissue damage. Researchers in China explored using CRISPR-Cas9 to edit HSV-1 in the treatment of HSK in mice, and blocked HSV-1 replication in human corneas. Previous studies using CRISPR-Cas9 or adeno-associated virus (AAV) vector were conducted in vitro, as compared to the present in vivo studies. The Shanghai researchers developed mRNA-carrying lentiviral particles "that simultaneously deliver SpCas9 [CRISPR-Cas9] mRNA and viral-gene-targeting guide RNAs (designated HSV-1-erasing lentiviral particles, termed HELP)." These particles move by retrograde transport to the trigeminal ganglia to target HSV-1 genomes directly. This approach is interesting in the sense that clearing neuronal reservoirs of latent HSV-1 could prevent the recurrence of HSK, as was shown in mice in this case. The researchers reported no significant side effects in the HELP-treated mice, and whole-genome sequencing of human-derived corneas infected with HSV-1 showed inhibited viral replication without causing off-target effects. Current treatments for HSK, such as acyclovir (ACV) and other anti-virals, inhibit DNA replication but do not prevent disease recurrence. The researchers think their findings "could support the potential clinical utility of HELP for treating refractory HSK."

My rating of this study: ⭐⭐

Yin D, Ling S, Wang D, et al. "Targeting herpes simplex virus with CRISPR–Cas9 cures herpetic stromal keratitis in mice." Nature Biotechnology.  39:567–577. 11 January 2021. https://doi.org/10.1038/s41587-020-00781-8