May 2003
Volume 44, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2003
Promoters as a Tool to Target Gene Expression into the Mouse Retina Using Subretinal Injection of Self-Inactivating Lentiviral Vectors
Author Affiliations & Notes
  • C. Kostic
    Oculogenetic Unit, Jules Gonin Eye Hosp, Lausanne, Switzerland
  • M. Jaquet
    Oculogenetic Unit, Jules Gonin Eye Hosp, Lausanne, Switzerland
  • P. Salmon
    Dept. of Genetic and Microbiology, University Medical Center (CMU), Geneva, Switzerland
  • N. Déglon
    The Neuroscience Institute, EPFL, Lausanne, Switzerland
  • P. Aebischer
    The Neuroscience Institute, EPFL, Lausanne, Switzerland
  • D.F. Schorderet
    Division of Medical Genetics, CHUV, Lausanne, Switzerland
  • F.L. Munier
    Division of Medical Genetics, CHUV, Lausanne, Switzerland
  • Y. Arsenijevic
    Division of Medical Genetics, CHUV, Lausanne, Switzerland
  • Footnotes
    Commercial Relationships  C. Kostic, None; M. Jaquet, None; P. Salmon, None; N. Déglon, None; P. Aebischer, None; D.F. Schorderet, None; F.L. Munier, None; Y. Arsenijevic, None.
  • Footnotes
    Support  Gebert Ruff, ProVisu and Swiss National Science Foundation
Investigative Ophthalmology & Visual Science May 2003, Vol.44, 448. doi:
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      C. Kostic, M. Jaquet, P. Salmon, N. Déglon, P. Aebischer, D.F. Schorderet, F.L. Munier, Y. Arsenijevic; Promoters as a Tool to Target Gene Expression into the Mouse Retina Using Subretinal Injection of Self-Inactivating Lentiviral Vectors . Invest. Ophthalmol. Vis. Sci. 2003;44(13):448.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose: Gene transfer appears to be a promising approach to prevent photoreceptor loss. However specific cell type targeting using particular promoters has not yet been extensively described for lentiviral vector delivery in the retina. In our previous studies, we described the activities of different promoters (phosphoglycerate kinase (PGK), elongation factor-1 (EFS) and rhodopsin (Rho) promoters) using intravitreous injection of self-inactivating lentiviral vectors in DBA/2 mice eyes (Kostic et al., Gene Therapy in press). Here we analyzed these promoter activities using subretinal injection, a site more favorable to target photoreceptors. Methods: Self-inactivated lentiviral vector preparations were subretinally injected into adult DBA/2 mice eyes (n=6 to 18). Cell transductions were observed 7 days post-injection. Results: Using intravitreous injections in adult DBA/2 mice, the PGK promoter expression pattern was shown to be predominant in RPE cells, the EFS promoter was also expressed in RPE cells and to a lesser extent in other retinal cells, while transduction with the Rho promoter is inefficient. In this new study, subretinal injections in adult mice restrain PGK and EFS expression pattern to RPE cells only, while the Rho promoter activity is this time observed in 3% of the photoreceptors around the injection site. Conclusion: Thus although RPE cells are easily transduced by self-inactivating lentiviral vectors, subretinal injections improve photoreceptor transduction. Additionally, using subretinal injections, both EFS and PGK promoters should be appropriate for delivery of a secreted survival factor to target adjacent degenerating photoreceptors, or for gene replacement in RPE cells. However further experiments have to be performed to improve photoreceptor transduction efficiency.

Keywords: gene transfer/gene therapy • retina • retinal pigment epithelium 
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