[Novel gene transfer using micellar nanovectors inhibits choroidal neovascularization]

Abstract

The treatment of age-related macular degeneration (AMD) caused by choroidal neovascularization (CNV) is difficult. More effective therapy for regulating CNV is needed. We demonstrated that intravenous nonviral vectors based on the complex of plasmid DNA with synthetic cationic polymers accumulate in choroidal neovascularization (CNV) with high efficiency through an enhanced the permeability and retention (EPR) effect. This review shows the results of in vivo angiogenic control by intravenous injection of a polyplex micelle-encapsulating plasmid vector using a mice CNV model. Polyion complex (PIC) micelles consisting of plasmid DNA and poly (ethylene glycol)-b-poly (N-[N-(2-aminoethyl)-2-aminoethyl] aspartamidef block copolymers [PEG-b-PAsp (DET)] were used. These show minimal cytotoxicity and high transfection efficiency both in vitro and in vivo, and have been utilized for gene therapy against a mouse corneal neovascularization model by local administration of plasmid-encoding soluble vascular endothelial growth factor receptor 1 (soluble Fms-like tyrosine kinase-1: sFlt-1). Transfection of plasmid-expressing sFlt-1 with PEG-C6-P[Asp (DET)] polyplex micelles by intravenous injection into mice CNV models showed significant inhibition of developing CNV. We found that nonviral gene therapy has significant potential for regulation of CNV using plasmids with PEG-C6-P [Asp (DET)] polyplex micelles.