Stable transgene expression in rod photoreceptors after recombinant adeno-associated virus-mediated gene transfer to monkey retina.
Recombinant adeno-associated virus (rAAV) is a promising vector for therapy of retinal degenerative diseases. We evaluated the efficiency, cellular specificity, and safety of retinal cell transduction in nonhuman primates after subretinal delivery of an rAAV carrying a cDNA encoding green fluorescent protein (EGFP), rAAV. CMV.EGFP. The treatment results in efficient and stable EGFP expression lasting >1 year. Transgene expression in the neural retina is limited exclusively to rod photoreceptors. There is neither electroretinographic nor histologic evidence of photoreceptor toxicity. Despite significant serum antibody responses to the vector, subretinal readministration results in additional transduction events. The findings further characterize the retinal cell tropism of rAAV. They also support the development of studies aimed ultimately at treating inherited retinal degeneration by using rAAV-mediated gene therapy.
Bennett
J
J
Department of Ophthalmology, F. M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, 51 North 39th Street, Philadelphia, PA 19104, USA. jebennet@mail.med.upenn.edu
Maguire
A M
AM
Cideciyan
A V
AV
Schnell
M
M
Glover
E
E
Anand
V
V
Aleman
T S
TS
Chirmule
N
N
Gupta
A R
AR
Huang
Y
Y
Gao
G P
GP
Nyberg
W C
WC
Tazelaar
J
J
Hughes
J
J
Wilson
J M
JM
Jacobson
S G
SG
D000818:Animals; D004274:DNA, Recombinant / Q000378:metabolism; D000229:Dependovirus; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins / Q000235:genetics; D008253:Macaca mulatta; D008856:Microscopy, Fluorescence; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism*; D012160:Retina / Q000378:metabolism*; D019076:Transgenes
D004274:DNA, Recombinant; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins