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

Dan J Von Seggern, Edith Aguilar, Karen Kinder, Shonna Kaye Fleck, J C Gonzalez Armas, Susan C Stevenson, Peter Ghazal, Glen R Nemerow, Martin Friedlander

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)27-34
Number of pages8
JournalMolecular Therapy
Volume7
Issue number1
Publication statusPublished - 2003

Keywords

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

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