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In vivo transduction of photoreceptors or ciliary body by intravitreal injection of pseudotyped adenoviral vectors

Von Seggern, Dan J, Aguilar, Edith, Kinder, Karen, Fleck, Shonna Kaye, Gonzalez Armas, J.C, Stevenson, Susan C, Ghazal, Peter, Nemerow, Glen R and Friedlander, Martin 2003. In vivo transduction of photoreceptors or ciliary body by intravitreal injection of pseudotyped adenoviral vectors. Molecular Therapy 7 (1) , pp. 27-34. 10.1016/S1525-0016(02)00030-8

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Strategies for retargeting adenoviral (Ad) vectors have been developed, but their in vivo efficacy remains to be demonstrated. Gene delivery to specific ocular cell types represents an approach to treating many diseases that cause irreversible blindness. One of these cell types, the photoreceptor (PR), is not infected by standard Ad5-based vectors. We evaluated gene delivery after intraocular injection of Ads pseudotyped with three different fiber proteins and found three distinct patterns of infection. An intravitreally injected Ad5 vector readily infected the iris, corneal endothelium, and ciliary body, while few cells in the retina expressed transgene product. In contrast, an Ad3-pseudotyped virus selectively transduced ciliary body, of interest for treating diseases such as glaucoma. A vector pseudotyped with the fiber protein of Ad37 transduced PRs as well as ciliary body. This finding has potential application to the treatment of retinal degenerative or neovascular diseases. These studies demonstrate cell type-selective gene delivery in vivo with retargeted Ads, provide information about the cellular tropisms of several Ad serotypes, and should lead to improved strategies for preserving vision.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Nature Publishing Group: Open Access Hybrid Model Option B
ISSN: 1525-0016
Last Modified: 30 Jul 2018 14:45

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