April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
Non Integrative Lentiviral Vectors for Gene Transfer in the Retina
Author Affiliations & Notes
  • S. Philippe
    Unit of Gene Therapy and Stem Cell Biology, Jules-Gonin Eye Hospital, Lausanne, Switzerland
    Laboratoire de Génétique Moléculaire de la Neurotransmission et des Processus Neurodégénératifs, CNRS UMR 7091, Paris, France
  • Y. Arsenijevic
    Unit of Gene Therapy and Stem Cell Biology, Jules-Gonin Eye Hospital, Lausanne, Switzerland
  • C. Kostic
    Unit of Gene Therapy and Stem Cell Biology, Jules-Gonin Eye Hospital, Lausanne, Switzerland
  • C. Serguera
    Laboratoire de Génétique Moléculaire de la Neurotransmission et des Processus Neurodégénératifs, CNRS UMR 7091, Paris, France
  • J. Mallet
    Laboratoire de Génétique Moléculaire de la Neurotransmission et des Processus Neurodégénératifs, CNRS UMR 7091, Paris, France
  • C. Sarkis
    Laboratoire de Génétique Moléculaire de la Neurotransmission et des Processus Neurodégénératifs, CNRS UMR 7091, Paris, France
  • Footnotes
    Commercial Relationships  S. Philippe, CNRS, P; Y. Arsenijevic, None; C. Kostic, None; C. Serguera, CNRS, P; J. Mallet, CNRS, P; C. Sarkis, CNRS, P.
  • Footnotes
    Support  European FP6, INTEGRA NEST-Adventure contract #29025; Retina France
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 3024. doi:
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      S. Philippe, Y. Arsenijevic, C. Kostic, C. Serguera, J. Mallet, C. Sarkis; Non Integrative Lentiviral Vectors for Gene Transfer in the Retina. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3024.

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

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Abstract

Purpose: : Lentiviral vectors are among the most efficient gene transfer tools for both dividing and non dividing cells, including pigmented epithelial cells of the retina. One of the latest developments in the field, which represents a significant advance in biosafety, consists in the use of non integrative lentiviral vectors (NILVs). These newly described tools were already shown to be efficient in various tissues, such as the retina. They allow prolonged transgene expression as long as the transduced cells do not divide or divide slowly. However, they were also shown to induce transgene expression less efficiently than their integrative counterparts. Further investigations are thus needed to improve their potential. To this aim, different strategies are under evaluation. In this study, we focused on using different integrase mutations.

Methods: : We considered different integrase mutations, including modifications in the catalytic site and in the C-terminal domain of the enzyme. Lentiviral vectors bearing these mutant integrases and allowing expression of various transgenes were produced and characterized in vitro and in vivo. In particular, we evaluated their transgene expression capability. Influence of integrase mutation on the residual integration activity was also investigated.

Results: : In line with the fact that the lentiviral integrase is involved in several steps of the replication cycle of lentiviruses, we observed that integrase mutations can modify lentiviral vector features, resulting in different transduction efficiencies as well as modulation of the integration activity.

Conclusions: : NILVs appear as suitable tools for gene transfer in the retina, particularly to transduce RPE cells. They can be advantageously used, for instance, to develop neuroprotective strategies aimed at rescuing photoreceptors from death in various retinal diseases.

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