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Persistent transgene product in retina, optic nerve and brain after intraocular injection of rAAV
Open accessAbstract
Recombinant adeno-associated virus (rAAV) is a promising vector for retinal application as it transduces photoreceptors and retinal pigment epithelium cells efficiently and in a stable fashion. Because rAAV also transduces retinal ganglion cells, we reasoned that ocular application of rAAV might result in delivery of transgenic protein to the CNS. Here we describe high levels of green fluorescent protein (GFP) persisting at least 6 months in optic nerves and brains of mice and dogs after intravitreal delivery of rAAV-GFP. There was no clinical or histological evidence of inflammatory response although a mild humoral Th-2 response to viral capsid proteins was detected. These findings have important implications with respect to therapeutic applications of rAAV.
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A previous study showed transgene expression in the optic nerve and brain after AAV2-GFP IVT injection.
“In addition, a previous study showed transgene expression in the optic nerve and brain after AAV2-GFP IVT injection (Dudus et al., 1999).”
From AAV2 and AAV9 tropism and transgene expression in the mouse eye and major tissues after intravitreal and subretinal delivery (2023) · cites this paper as Dudus et al., 1999
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Metadata
- Authors
- Dudus, L., Anand, V., Acland, G. M., Chen, S.-J., Wilson, J. M., Fisher, K. J., Maguire, A. M., & Bennett, J.
- Affiliations
- University of Pennsylvania (US)
- Cornell University (US)
- Tulane University (US)
- Corresponding author
- Bennett, Jean
- Venue
- Vision Research
- Publisher
- Elsevier BV
- Published
- 1999-07
- Volume
- 39
- Issue
- 15
- Pages
- 2545-2553
- ISSN
- 0042-6989 (ISSN-L)
- OpenAlex
- W1973389197
- Cited by
- 160
- References
- 11
- Citations by year
- 2025: 4 · 2024: 4 · 2023: 2 · 2022: 4 · 2021: 3 · 2020: 2 · 2019: 4 · 2018: 5 · 2017: 7 · 2016: 4 · 2015: 5 · 2014: 1 · 2013: 2 · 2012: 7
- FWCI
- 5.41
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Vision Research (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- F. M. Kirby Foundation
- Research to Prevent Blindness
- James N. Kirby Foundation
- National Eye Institute (EY10820, R01 EY10820, EY 06855, R01EY010820)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Health Sciences › Medicine › Ophthalmology › Retinal Development and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- recombinant adeno-associated virus, intravitreal injection, transgene persistence, retinal ganglion cells, optic nerve, transneuronal spread, capsid protein, retinal gene therapy, photoreceptors, retinal pigment epithelium
- MeSH terms
- Dependovirus, Animals, Antibodies, Viral, Brain, Dogs, Enzyme-Linked Immunosorbent Assay, Fluorescence, Indicators and Reagents, Luminescent Proteins, Optic Nerve, Photoreceptor Cells, Pigment Epithelium of Eye, Recombinant Proteins, Retina, Transduction, Genetic, Blotting, Western, Gene Expression, Transgenes, Green Fluorescent Proteins, Mice
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