Reduction of fibronectin expression by intravitreal administration of antisense oligonucleotides

Sayon Roy, Kathy Zhang, Timothy Roth, Sergei Vinogradov, Richard S. Kao, Alexander Kabanov

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

We have investigated whether antisense oligonucleotides delivered intravitreally could reduce gene expression specifically in the retina. In this study, phosphorothioate antisense oligonucleotides targeted to fibronectin transcripts were coupled to a novel carrier and used to specifically reduce fibronectin (FN) expression in retinal vascular cells. Using confocal microscopy, fluorescence from fluorescein isothiocyanate- labeled FN-oligonuoleotides was detected in retinal vascular cells at 24 h postinjection and persisted until day 6 (the end point of this study). The fibronectin mRNA level was consistently decreased to 86.7% ± 7.9% of control (p<0.05) at day 2, and 46.7% ±4.9% of control (p<0.01) at day 6. In contrast, the β-actin mRNA level, an internal control, was unaltered in rat retinas that received FN-oligonucleotides. Fibronectin protein level at day 6 was also significantly reduced to 61.4% ± 16% of control (p<0.01). No toxic effect resulting from the carrier was detected histologically. Thus, intravitreal delivery of antisense oligonucleotides to modulate abnormal gene expression in retinal diseases may be an effective approach for ocular gene therapy.

Original languageEnglish (US)
Pages (from-to)476-479
Number of pages4
JournalNature Biotechnology
Volume17
Issue number5
DOIs
StatePublished - May 1 1999

Keywords

  • Antisense oligonucleotides
  • Basement membrane
  • Block copolymer
  • Gene therapy

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering

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    Roy, S., Zhang, K., Roth, T., Vinogradov, S., Kao, R. S., & Kabanov, A. (1999). Reduction of fibronectin expression by intravitreal administration of antisense oligonucleotides. Nature Biotechnology, 17(5), 476-479. https://doi.org/10.1038/8654