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

• DOI: 10.1002/mabi.201500192
• Publication Date: 2015-08-13T19:03:22Z
• Authors: Da Sun; Hiroshi Maeno; Maneesh Gujrati; Rebecca Schur; Akiko Maeda; Tadao Maeda; Krzysztof Palczewski; Zheng‐Rong Lu
• Keywords: 0301 basic medicine; Dendrimers; Mice, Inbred BALB C; DNA plasmid; Gene Transfer Techniques; ECO lipid; nanoglobule; subretinal gene delivery; DNA; Lipids; Retina; Cell Line; Mice; 03 medical and health sciences; Genes; Genes, Reporter; Materials Testing; Animals; Nanoparticles; gene delivery; Reporter; Inbred BALB C

AbstractDevelopment 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.