Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Balaggan, KS; Binley, K; Esapa, M; Iqball, S; Askham, Z; Kan, O; Tschernutter, M; Bainbridge, JW; Naylor, S; Ali, RR.
Stable and efficient intraocular gene transfer using pseudotyped EIAV lentiviral vectors.
J Gene Med. 2006; 8(3): 275-285.
Doi: 10.1002/jgm.845
Web of Science
PubMed
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- Co-Autor*innen der Med Uni Graz
- Tschernutter Marion
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- Abstract:
- We have developed minimal non-primate lentiviral vectors based on the equine infectious anaemia virus (EIAV). We evaluated the in vivo expression profiles of these vectors delivered regionally to ocular tissues to define their potential utility in ocular gene therapy. EIAV vectors pseudotyped with VSV-G or rabies-G envelope proteins were delivered subretinally, intravitreally or into the anterior chambers (intracameral administration) in mice. Reporter gene (eGFP) expression was analysed using in vivo retinal imaging or histological examination of eyes and brains at intervals between 3 days and 16 months. We investigated the effects of vector titre, pseudotype, genome configuration, site of intraocular administration, intentional retinal trauma and the degree of retinal maturation on the spatial and temporal expression profiles of these vectors. Subretinal vector delivery resulted in efficient and stable transduction of retinal pigment epithelial (RPE) cells and variable transduction of photoreceptors up to 16 months post-injection. Retinal trauma facilitated the local transduction of neurosensory retinal cells. Intracameral administration of VSV-G- but not rabies-G-pseudotyped vectors produced stable eGFP expression in corneal endothelial cells and trabecular meshwork. The cellular tropism and expression kinetics of optimised EIAV vectors after intraocular administration make them attractive vehicles for delivering therapeutic genes in the management of inherited and acquired retinal and anterior segment disorders.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Female -
- Gene Expression Profiling -
- Gene Transfer Techniques -
- Genes, Reporter -
- Genetic Therapy - methods
- Genetic Vectors -
- Genome -
- Green Fluorescent Proteins - biosynthesis
- Infectious Anemia Virus, Equine - genetics
- Kinetics -
- Mice -
- Mice, Inbred C57BL -
- Photoreceptor Cells -
- Pigment Epithelium of Eye - physiology
- Retina - injuries
- Retinal Diseases - genetics Retinal Diseases - therapy
- Transduction, Genetic -
- Tropism -
- Find related publications in this database (Keywords)
- EIAV
- gene therapy
- lentivirus
- retinal pigment epithelium
- photoreceptors
- cornea