Persistent transgene product in retina, optic nerve and brain after intraocular injection of rAAV

• Published in: Vision research (Oxford) Vol. 39; no. 15; pp. 2545 - 2553
• Main Authors: Dudus, Lorita, Anand, Vibha, Acland, Gregory M, Chen, Shu-Jen, Wilson, James M, Fisher, Krishna J, Maguire, Albert M, Bennett, Jean
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Oxford Elsevier Ltd 01.07.1999; Elsevier Science
• Subjects: Animals; Antibodies, Viral - biosynthesis; Biological and medical sciences; Biotechnology; Blotting, Western; Brain - metabolism; Dependovirus - immunology; Dogs; Enzyme-Linked Immunosorbent Assay; Fluorescence; Fundamental and applied biological sciences. Psychology; Ganglion cells; Gene Expression; Gene therapy; Green Fluorescent Proteins; Health. Pharmaceutical industry; Immune response; Indicators and Reagents; Industrial applications and implications. Economical aspects; Lateral geniculate nucleus; Luminescent Proteins - biosynthesis; Mice; Optic Nerve - metabolism; Optic nerve tract; Photoreceptor Cells - chemistry; Pigment Epithelium of Eye - chemistry; Recombinant Proteins; Retina - metabolism; Transduction, Genetic; Transgenes; Optic nerve tract; Immune response; Lateral geniculate nucleus; Gene therapy; Ganglion cells; Fissipedia; Carnivora; Optic nerve; Recombinant virus; Rodentia; Central nervous system; Retina; Eye; Visual system; Ganglion neuron; Vertebrata; Mammalia; Visual pathway; Mouse; Animal; Vision; Perception; Recombinant protein; Dog; Brain (vertebrata)
• ISSN: 0042-6989; 1878-5646
• DOI: 10.1016/S0042-6989(98)00308-3

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.