Abstract
We report on the long-term safety of AAV2.sFlt-1 (a recombinant adeno-associated virus serotype 2 carrying the soluble form of the Flt-1 receptor) injection into the subretinal space of non-human primates. Levels of sFlt-1 protein were significantly higher (P0.05) in the vitreous of four out of five AAV2.sFlt-1-injected eyes. There was no evidence of damage to the eyes of animals that received subretinal injections of AAV2.sFlt-1; ocular examination showed no anterior chamber flare, normal fundus and electroretinography responses equivalent to those observed before treatment. Notably, immunological analysis demonstrated that gene therapy involving subretinal injection of AAV2.sFlt-1 does not elicit cell-mediated immunity. Biodistribution analysis showed that AAV2.sFlt-1 could be detected only in the eye and not in the other organs tested. These data indicate that gene therapy with subretinal AAV2.sFlt-1 is safe and well tolerated, and therefore promising for the long-term treatment of neovascular diseases of the eye.
Original language | English (US) |
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Pages (from-to) | 999-1009 |
Number of pages | 11 |
Journal | Gene Therapy |
Volume | 19 |
Issue number | 10 |
DOIs | |
State | Published - Oct 2012 |
Externally published | Yes |
Keywords
- Immunology
- Neovascularization
- Retinal diseases
ASJC Scopus subject areas
- Molecular Medicine
- Molecular Biology
- Genetics