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Meganuclease targeting HSV‐1 limits viral endothelitis in vivo
Author(s) -
CHAPELLIER B,
LABETOULLE M,
GAILLEDRAT M,
GABISON E
Publication year - 2012
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2012.2631.x
Subject(s) - biology , virus , microbiology and biotechnology , in vivo , virology , recombinant dna , gene , genetics
Purpose The aim of this study is to assess the antiviral property of a meganuclease targeting HSV‐1 in the prevention of HSV endothelitis in a newly develloped rabbit in vivo model. Methods NZW received intracamerular injection of recombinant adeno‐associated virus equipped with a constitutive expression cassette containing either the meganuclease gene or a non‐coding sequence. After treatment with intravitreal triamcinolone acetonide, HSV‐1 F(1) virus recombinant for LacZ reporter was injected in the inner chamber of the eye,for an analysis 2 days later. Corneal edema, keratic precipitates and the number of contamination plaques were evaluated. Results In 4 tests with 24 experimental or control corneas, the meganuclease‐treated groups systematically showed a decrease in their average number of contamination plaques while compared to controls (from 15 to 71%). Presence of protein and inflammatory cells in the aqueous humor or at the endothelium surface, as well as the extension of focal edema, was also limited by the endonuclease. Conclusion Meganuclease gene therapy targeting HSV‐1 DNA restricts degradation of the endothelium initiated by HSV‐1 injection.