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Targeting herpes simplex virus with CRISPR-Cas9 cures herpetic stromal keratitis in mice.

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 from the site of infection or latent reservoirs in the trigeminal ganglia. Here, we target HSV-1 genomes directly using mRNA-carrying lentiviral particles that simultaneously deliver SpCas9 mRNA and viral-gene-targeting guide RNAs (designated HSV-1-erasing lentiviral particles, termed HELP). We show that HELP efficiently blocks HSV-1 replication and the occurrence of herpetic stromal keratitis (HSK) in three different infection models. HELP was capable of eliminating the viral reservoir via retrograde transport from corneas to trigeminal ganglia. Additionally, HELP inhibited viral replication in human-derived corneas without causing off-target effects, as determined by whole-genome sequencing. These results support the potential clinical utility of HELP for treating refractory HSK.

SUBMITTER: Yin D

PROVIDER: S-EPMC7611178 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Targeting herpes simplex virus with CRISPR-Cas9 cures herpetic stromal keratitis in mice.

Yin Di D Ling Sikai S Wang Dawei D Dai Yao Y Jiang Hao H Zhou Xujiao X Paludan Soren R SR Hong Jiaxu J Cai Yujia Y

Nature biotechnology 20210111 5

Herpes simplex virus type 1 (HSV-1) is a leading cause of infectious blindness. Current treatments for HSV-1 do not eliminate the virus from the site of infection or latent reservoirs in the trigeminal ganglia. Here, we target HSV-1 genomes directly using mRNA-carrying lentiviral particles that simultaneously deliver SpCas9 mRNA and viral-gene-targeting guide RNAs (designated HSV-1-erasing lentiviral particles, termed HELP). We show that HELP efficiently blocks HSV-1 replication and the occurren ...[more]

PMID: 33432198

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