Self-Assembly of a Multifunctional Lipid With Core-Shell Dendrimer DNA Nanoparticles Enhanced Efficient Gene Delivery at Low Charge Ratios into RPE Cells.
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.
Department of Biomedical Engineering, School of Engineering, Case Western Reserve University, Cleveland, Ohio , 44140, USA.
Da
D
Sun
Department of Ophthalmology, School of Medicine, Case Western Reserve University, Cleveland, Ohio, 44140, USA.
Hiroshi
H
Maeno
Department of Biomedical Engineering, School of Engineering, Case Western Reserve University, Cleveland, Ohio , 44140, USA.
Maneesh
M
Gujrati
Department of Biomedical Engineering, School of Engineering, Case Western Reserve University, Cleveland, Ohio , 44140, USA.
Rebecca
R
Schur
Department of Ophthalmology, School of Medicine, Case Western Reserve University, Cleveland, Ohio, 44140, USA.|Department of Pharmacology, Cleveland Center for Membrane and Structural Biology, School of Medicine, Case Western Reserve University, Cleveland, Ohio, 44140, USA.
Akiko
A
Maeda
Department of Ophthalmology, School of Medicine, Case Western Reserve University, Cleveland, Ohio, 44140, USA.
Tadao
T
Maeda
Department of Pharmacology, Cleveland Center for Membrane and Structural Biology, School of Medicine, Case Western Reserve University, Cleveland, Ohio, 44140, USA.
Krzysztof
K
Palczewski
Department of Biomedical Engineering, School of Engineering, Case Western Reserve University, Cleveland, Ohio , 44140, USA. zxl125@case.edu.
Zheng-Rong
ZR
Lu
D000818:Animals; D002460:Cell Line; D004247:DNA / Q000737:chemistry*; D050091:Dendrimers / Q000737:chemistry*; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D008055:Lipids / Q000737:chemistry*; D008422:Materials Testing; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D012160:Retina / Q000166:cytology / Q000378:metabolism
D050091:Dendrimers; D008055:Lipids; D004247:DNA
DNA plasmid; ECO lipid; gene delivery; nanoglobule; subretinal gene delivery