Gene transfer using micellar nanovectors inhibits corneal neovascularization in vivo
Aya Iriyama1, Tomohiko Usui, Yasuo Yanagi
1Department of Ophthalmology, University of Tokyo School of Medicine, Bunkyo-ku, Tokyo, Japan. akagi-tky@umin.ac.jp
Purpose:
The efficacy of gene therapy using nonviral vector based on polyplex micelle has been studied against corneal neovascularization in mice.
Methods:
A block copolymer, poly(ethylene glycol) (PEG)-block-polycation carrying ethylenediamine units in the side chain (PEG-b-P[Asp(DET)]), was prepared. PEG-b-P[Asp(DET)] formed a polyplex micelle through the polyion complex formation with plasmid DNA. To evaluate in vivo gene transfer efficiency, PEG-b-P[Asp(DET)] micelle was injected into the subconjunctival space of mice, and the expression of the reporter gene was assessed. Furthermore, mouse corneal neovascularization models were treated with the PEG-b-P[Asp(DET)] polyplex micelle containing expression plasmid vector of soluble vascular endothelial growth factor receptor 1 (sflt-1).
Results:
Subconjunctival injection of the PEG-b-P[Asp(DET)] polyplex micelle containing a reporter gene showed prolonged gene expression with low cytotoxicity. Also, gene transfer into subconjunctival space by the polyplex micelle containing sflt-1 plasmid showed significant inhibition of corneal neovascularization in mice.
Conclusions:
Nonviral gene therapy using PEG-b-P[Asp(DET)] polyplex micelle may have potential for safe and effective therapeutic treatment of corneal neovascularization.
