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In vivo gene transfer to the rat retina using herpes simplex virus type 1 (HSV-1)-based amplicon vectors

Gene Therapy volume 12, pages 1283–1288 (2005)Cite this article

Abstract

The purpose of our study was to evaluate the transduction profiles of herpes simplex virus type 1 (HSV-1)-based amplicon vectors following subretinal injection in the rat. Two amplicon vectors were tested, pHy-CMVGFP and pHy-RPEGFP, both carrying the green fluorescent protein (GFP) under the control of the cytomegalovirus (CMV) ubiquitous promoter or the RPE65-specific promoter, respectively. For the two amplicon vectors, the GFP reporter gene was efficiently expressed in retinal pigment epithelial (RPE) cells but not in the adjacent photoreceptors. GFP expression was maximum as early as 2 days postadministration but decreased over time to become almost undetectable at 6 weeks postinjection. Supertransduction with a second amplicon vector, pHSVlac, reactivated expression of GFP in approximately 10% of the cells initially transduced at 2 days postinjection of pHy-CMVGFP or pHy-RPEGFP. Reactivation of transgene expression was transient, no GFP signal was detected 8 days after pHSVlac injection. In conclusion, HSV-1 amplicon vectors allow rapid and efficient, but transient, gene transfer in RPE cells following subretinal injection.

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Acknowledgements

We thank Anna Skulimowski for critical reading and editing. We thank Robin Ali for providing the RPE65 promoter construct. This work was supported by the Association Française contre les Myopathies (AFM), the INSERM, the Fondation pour la Thérapie Génique en Pays de la Loire, the Lions Clubs International Foundation (LCIF) and the Swiss National Science Foundation No. 3100A0-100195 (CF).

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Authors and Affiliations

  1. Institute of Virology, University of Zurich, Zurich, Switzerland

    C Fraefel & M Ackermann

  2. INSERM UMR U649, Bat. J. Monnet, 30 Avenue J. Monnet, Nantes Cedex, France

    A Mendes-Madeira, O Mabon, A Lefebvre, G Le Meur, P Moullier & F Rolling

  3. EFS-Pays de la Loire, Nantes, France

    P Moullier

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  1. C Fraefel
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Fraefel, C., Mendes-Madeira, A., Mabon, O. et al. In vivo gene transfer to the rat retina using herpes simplex virus type 1 (HSV-1)-based amplicon vectors. Gene Ther 12, 1283–1288 (2005). https://doi.org/10.1038/sj.gt.3302553

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