title: AAV9 targets cone photoreceptors in the nonhuman primate retina.
abstract: Transduction of retinal pigment epithelial cells with an adeno-associated viral vector (AAV) based on serotype 2 has partially corrected retinal blindness in Leber congenital amaurosis type 2. However, many applications of gene therapy for retinal blindness rely on the efficient transduction of rod and cone photoreceptor which is difficult to achieve with first generation vector technology. To address this translational need, we evaluated rod and cone photoreceptor targeting of 4 novel AAV capsids (AAV7, AAV9, rh.64R1 and rh.8R) versus AAV2 and AAV8 in a foveated retina. Eyes of 20 nonhuman primates were injected subretinally in the proximity of the fovea. While numerous vectors efficiently transduced rods, only AAV9 targeted cones both centrally and peripherally efficiently at low doses, likely due to the abundance of galactosylated glycans, the primary receptor for AAV9, on cone photoreceptors. We conclude AAV9 is an ideal candidate for strategies that require restoration of cone photoreceptor function.
authors: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America. luk_vandenberghe@meei.harvard.edu
authors: Luk H
authors: LH
authors: Vandenberghe
authors: Peter
authors: P
authors: Bell
authors: Albert M
authors: AM
authors: Maguire
authors: Ru
authors: R
authors: Xiao
authors: Tim B
authors: TB
authors: Hopkins
authors: Rebecca
authors: R
authors: Grant
authors: Jean
authors: J
authors: Bennett
authors: James M
authors: JM
authors: Wilson
mesh_terms: D000818:Animals; D000229:Dependovirus / Q000235:genetics; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000627:therapeutic use; D057130:Leber Congenital Amaurosis / Q000235:genetics / Q000628:therapy; D011323:Primates; D012160:Retina / Q000166:cytology / Q000503:physiopathology; D017949:Retinal Cone Photoreceptor Cells / Q000473:pathology*; D017948:Retinal Rod Photoreceptor Cells / Q000473:pathology*; D014161:Transduction, Genetic
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