The potential of recombinant adeno-associated virus-mediated secretion gene therapy for the treatment of ocular neovascularization

Yvonne Kim Yen Lai

Research output: ThesisDoctoral Thesis

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Abstract

[Truncated] Age-related macular degeneration (AMD) is the leading cause of irreversible blindness among the elderly in developed countries. However, current conventional treatments have limited application and efficacies. Gene therapy that can mediate long term delivery of therapeutic agents might offer a more comprehensive, effective and potentially permanent treatment. In particular, the treatment of abnormalities in retinal pigment epithelial (RPE) cells, which have been implicated in the pathology of AMD and various other retinal disorders, might prevent or slow disease progression. However, central to the success of gene therapy is the efficient and stable delivery of therapeutic genes into the cells of interest. Recombinant adeno-associated virus (rAAV) has been shown to be a promising vector for transfer of genes into various types of cells.
In this thesis, an AAV-CMV.gfp vector, based on AAV type 2, encoding the green fluorescent protein (GFP) was generated to study rAAV transduction in ocular cells. In particular, the kinetics, potential mechanisms and stability of rAAV transduction in RPE cells in vitro were investigated. RPE cells were found to be highly permissive to AAV-CMV.gfp transduction in vitro, which might be related to an enhanced rate of second-strand synthesis in these cells. Analysis of AAV-CMV.gfp­ transduced RPE clones indicated that there was long-term expression of GFP in these cells, which was due to random single copy vector integration into the chromosome.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • The University of Western Australia
DOIs
Publication statusUnpublished - 2002

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