Meganuclease targeting HSV-1 protects against herpetic keratitis: Application to corneal transplants.

ABSTRACT: Herpes simplex virus (HSV) infection is a leading cause of corneal blindness. However, keratoplasty is only rarely proposed due to the high frequency of graft failure and associated recurrences. Gene therapy of the corneal graft might provide sustained protection against HSV infection. To test that hypothesis, we designed a meganuclease specific to an HSV-1 DNA sequence coding for major capsid protein (UL19) and selected an adeno-associated virus type-2 as the vector. Meganuclease was transduced into corneas and its effect was challenged in vitro, ex vivo, and then in vivo in a rabbit HSV-1-infection model of stromal keratitis and endotheliitis. In vivo, meganuclease exposure resulted in fewer infected stromal and endothelial cells, and protected against corneal

SUBMITTER: Chapellier B 

PROVIDER: S-EPMC9682361 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature