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

Academic Article
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Overview

authors

  • Von Seggern, D. J.
  • Aguilar, E.
  • Kinder, K.
  • Fleck, S. K.
  • Armas, J. C. G.
  • Stevenson, S. C.
  • Ghazal, Peter
  • Nemerow, Glen
  • Friedlander, Martin

publication date

  • January 2003

journal

  • Molecular Therapy  Journal

abstract

  • 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.

subject areas

  • Adenoviridae
  • Animals
  • Ciliary Body
  • Female
  • Genetic Vectors
  • Mice
  • Mice, Inbred BALB C
  • Photoreceptor Cells, Vertebrate
  • Transduction, Genetic
  • Vitreous Body
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Research

keywords

  • adenovirus
  • gene transfer
  • in vivo
  • intravitreal
  • ocular
  • photoreceptor
  • pseudotype
  • retina
  • targeting
  • tropism
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Identity

International Standard Serial Number (ISSN)

  • 1525-0016

Digital Object Identifier (DOI)

  • 10.1016/s1525-0016(02)00030-8

PubMed ID

  • 12573615
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Additional Document Info

start page

  • 27

end page

  • 34

volume

  • 7

issue

  • 1

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