Persistent transgene product in retina, optic nerve and brain after intraocular injection of rAAV.
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.
Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, School of Medicine, Stellar-Chance Laboratories, Philadelphia 19104-6069, USA.
L
L
Dudus
V
V
Anand
G M
GM
Acland
S J
SJ
Chen
J M
JM
Wilson
K J
KJ
Fisher
A M
AM
Maguire
J
J
Bennett
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D000229:Dependovirus / Q000276:immunology; D004285:Dogs; D004797:Enzyme-Linked Immunosorbent Assay; D005453:Fluorescence; D015870:Gene Expression; D049452:Green Fluorescent Proteins; D007202:Indicators and Reagents; D008164:Luminescent Proteins / Q000096:biosynthesis; D051379:Mice; D009900:Optic Nerve / Q000378:metabolism*; D010786:Photoreceptor Cells / Q000737:chemistry; D010857:Pigment Epithelium of Eye / Q000737:chemistry; D011994:Recombinant Proteins; D012160:Retina / Q000378:metabolism*; D014161:Transduction, Genetic; D019076:Transgenes
D000914:Antibodies, Viral; D007202:Indicators and Reagents; D008164:Luminescent Proteins; D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins