期刊
NATURE BIOTECHNOLOGY
卷 39, 期 5, 页码 567-577出版社
NATURE PORTFOLIO
DOI: 10.1038/s41587-020-00781-8
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资金
- National Natural Science Foundation of China [31971364, 81970766, 81670818]
- Pujiang Talent Project of Shanghai [18PJ1404500]
- Natural Science Foundation of Shanghai [18ZR1419300]
- Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University [WF220441504]
- Shanghai Rising-Star Program [18QA1401100]
- Shanghai Innovation Development Program [2020779]
- Shanghai Key Clinical Research Program [SHDC2020CR3052B]
- European Research Council (ERC-AdG ENVISION) [786602]
- European Research Council (ERC) [786602] Funding Source: European Research Council (ERC)
The study targeted HSV-1 genomes directly using mRNA-carrying lentiviral particles (HELP), which efficiently blocked HSV-1 replication and reduced the occurrence of HSK in three different infection models. HELP was capable of eliminating the viral reservoir via retrograde transport from corneas to trigeminal ganglia, while inhibiting viral replication in human-derived corneas without causing off-target effects.
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.
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