부산대학교 도서관

Purpose Current anti‐viral treatments of Herpes simplex virus type 1 (HSV1) inhibit the viral replication but do not impair the latent form of the virus. This could be addressed by rare cutting endonucleases, such as meganucleases. The aim of this study was to demonstrate the antiviral activity of a HSV1‐specific meganuclease in a mouse model of herpes keratitis. Methods Three weeks after bilateral subconjunctival inoculation of recombinant associated‐adenovirus (rAAV) encoding either a HSV1‐specific meganuclease or a reporter gene (GFP), both cornea of mice were inoculated with a wild‐type HSV1 strain. Mice were sacrificed 6 or 28 days later and corneas were analyzed for the presence of HSV1 genome and viral transcripts. Results At 6 dpi, there was no clinical difference in the rate of acute herpetic keratitis, but the amounts of viral products were lower in mice treated with meganuclease‐encoding rAAV. At 28 dpi (stage of HSV1 latency), the rate of clear cornea was more important in the mice treated with meganuclease (p = 0.03), and the amounts of viral genome and transcripts were significantly less important (p<0.01. Conclusion The transduction of HSV1‐specific meganucleases in the ocular tissues by means of a subconjunctival inoculation of r‐AAV is associated with an improvement of corneal recovery, and a reduction in the viral load and replication in the cornea. These results suggest that specific meganucleases could be qualified as a new class of antiviral agent, with the potential to address replicative as well as latent viral DNA. Commercial interest [ABSTRACT FROM AUTHOR]