Gene transfer of an engineered zinc finger protein enhances the anti-angiogenic defense system

Katsutoshi Yokoi, Huanda Steve Zhang, Shu Kachi, Kamaljit S. Balaggan, Qi Yu, Dmitry Guschin, Mike Kunis, Richard Surosky, Liza M. Africa, James W. Bainbridge, Sharon Kaye Spratt, Philip D. Gregory, Robin R. Ali, Peter A. Campochiaro

Research output: Contribution to journalArticlepeer-review

Abstract

Zinc finger protein transcription factors (ZFP TFs) have been shown to positively or negatively regulate the expression of endogenous genes involved in a number of different disease processes. In this study we investigated whether gene transfer of an engineered ZFP TF designed to up-regulate expression of the chromosomal pigment epithelium-derived factor (Pedf) gene could suppress experimentally induced choroidal neovascularization (CNV). Transient transfection with engineered ZFP TFs significantly increased both Pedf messenger RNA (mRNA) and secreted PEDF protein levels in cell culture. Six weeks after intravitreous or subretinal injection of an adeno-associated viral (AAV) vector expressing the PEDF-activating ZFP TF in mice, we observed increased retinal Pedf mRNA, and a significant reduction in the size of CNV at Bruch's membrane rupture sites, assessed in vivo by fluorescein angiography or by postmortem measurements on choroidal flat mounts. Importantly, the anti-angiogenic activity persisted at 3 months after intravitreous injection. These data suggest that ZFP TF-driven enhancement of the endogenous anti-angiogenic defense system may provide a new approach for prophylaxis and treatment of neovascular diseases of the eye.

Original languageEnglish (US)
Pages (from-to)1917-1923
Number of pages7
JournalMolecular Therapy
Volume15
Issue number11
DOIs
StatePublished - Nov 2007

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

Fingerprint Dive into the research topics of 'Gene transfer of an engineered zinc finger protein enhances the anti-angiogenic defense system'. Together they form a unique fingerprint.

Cite this