Self-Assembly of a Multifunctional Lipid With Core-Shell Dendrimer DNA Nanoparticles Enhanced Efficient Gene Delivery at Low Charge Ratios into RPE Cells

Macromol Biosci. 2015 Dec;15(12):1663-72. doi: 10.1002/mabi.201500192. Epub 2015 Aug 13.

Abstract

Development of safe and effective gene delivery systems is essential in treating ocular genetic disorders. A hybrid nonviral system composed of a multifunctional lipid ECO and a G4 nanoglobule was designed for efficient gene delivery into RPE cells at low charge ratios. This system formed stable DNA nanoparticles at low N/P ratios, exhibited low cytotoxicity, and induced higher GFP expression in ARPE-19 cells at N/P = 6. The hybrid nanoparticles mediated significant reporter gene GFP expression ex-vivo in the retina from wild type C57 mice and in vivo in BALB/c mice. These hybrid nanoparticles are promising for in vitro and in vivo gene delivery at low charge ratios.

Keywords: DNA plasmid; ECO lipid; gene delivery; nanoglobule; subretinal gene delivery.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Line
  • DNA / chemistry*
  • Dendrimers / chemistry*
  • Gene Transfer Techniques*
  • Genes, Reporter
  • Lipids / chemistry*
  • Materials Testing*
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles / chemistry*
  • Retina / cytology
  • Retina / metabolism

Substances

  • Dendrimers
  • Lipids
  • DNA