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Intracorneal delivery of HSV-targeting CRISPR/Cas9 mRNA prevents herpetic stromal keratitis

Yin, D.; Ling, S.; Wang, D.; Jiang, H.; Paludan, S. R.; Hong, J.; Cai, Y.

2020-02-10 bioengineering
10.1101/2020.02.08.934125 bioRxiv
Show abstract

Herpes simplex virus type 1 (HSV-1) is a leading cause of infectious blindness. Current treatments for HSV-1 do not eliminate the virus and are incapable of modulating the virus reservoir. Here, we target HSV-1 genome directly using mRNA-carrying lentiviral particle (mLP) that simultaneously delivers spCas9 mRNA and two viral genes-targeting gRNAs (designated HSV-1-erasing lentiviral particles, HELP). We showed HELP efficiently blocked HSV-1 replication in both acute and recurrent infection models, and prevented occurrence of herpetic stromal keratitis (HSK). We further showed retrograde transportation of HELP from corneas to trigeminal ganglia (TG) where HSV-1 established latency and found evidence of HELP modulating herpes reservoir. Additionally, the potent antiviral activity of HELP was also replicable in human-derived corneas. These results strongly support clinical development of HELP as a new antiviral therapy and may accelerate mRNA-based CRISPR therapeutics.

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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.