BACKGROUND: Non-viral methods of gene delivery have been an attractive alternative to virus-based gene therapy. However, the vectors that are currently available have drawbacks limiting their therapeutic application. METHODS: We have developed a self-assembled non-viral gene carrier, poly-L-lysine modified iron oxide nanoparticles (IONP-PLL), which is formed by modifying poly-L-lysine to the surface of iron oxide nanoparticles. The ability of IONP-PLL to bind DNA was determined by ratio-dependent retardation of DNA in the agarose gel and co-sedimentation assay. In vitro cytotoxic effects were quantified by MTT assay. The transfection efficiency in vitro was evaluated by delivering exogenous DNA to different cell lines using IONP-PLL. Intravenous injection of IONP-PLL/DNA complexes into mice was evaluated as a gene delivery system for gene therapy. The PGL2-control gene encoding firefly luciferase and the EGFP-C2 gene encoding green fluorescent protein were used as marker genes. RESULTS: IONP-PLL could bind and protect DNA. In contrast to PLL and cationic liposomes, IONP-PLL described here was less cytotoxic in a broad range of concentrations. In the current study, we have demonstrated that IONP-PLL can deliver exogenous gene to cells in vitro and in vivo. After intravenous injection, IONP-PLL transferred reporter gene EGFP-C2 to lung, brain, spleen and kidney. Furthermore, we have demonstrated that IONP-PLL transferred exogenous DNA across the blood-brain barrier to the glial cells and neuron of brain. CONCLUSIONS: IONP-PLL, a low-toxicity vector, appears to have potential for fundamental research and genetic therapy in vitro and in vivo, especially for gene therapy of CNS disease. Copyright 2003 John Wiley & Sons, Ltd.
BACKGROUND: Non-viral methods of gene delivery have been an attractive alternative to virus-based gene therapy. However, the vectors that are currently available have drawbacks limiting their therapeutic application. METHODS: We have developed a self-assembled non-viral gene carrier, poly-L-lysine modified iron oxide nanoparticles (IONP-PLL), which is formed by modifying poly-L-lysine to the surface of iron oxide nanoparticles. The ability of IONP-PLL to bind DNA was determined by ratio-dependent retardation of DNA in the agarose gel and co-sedimentation assay. In vitro cytotoxic effects were quantified by MTT assay. The transfection efficiency in vitro was evaluated by delivering exogenous DNA to different cell lines using IONP-PLL. Intravenous injection of IONP-PLL/DNA complexes into mice was evaluated as a gene delivery system for gene therapy. The PGL2-control gene encoding firefly luciferase and the EGFP-C2 gene encoding green fluorescent protein were used as marker genes. RESULTS: IONP-PLL could bind and protect DNA. In contrast to PLL and cationic liposomes, IONP-PLL described here was less cytotoxic in a broad range of concentrations. In the current study, we have demonstrated that IONP-PLL can deliver exogenous gene to cells in vitro and in vivo. After intravenous injection, IONP-PLL transferred reporter gene EGFP-C2 to lung, brain, spleen and kidney. Furthermore, we have demonstrated that IONP-PLL transferred exogenous DNA across the blood-brain barrier to the glial cells and neuron of brain. CONCLUSIONS: IONP-PLL, a low-toxicity vector, appears to have potential for fundamental research and genetic therapy in vitro and in vivo, especially for gene therapy of CNS disease. Copyright 2003 John Wiley & Sons, Ltd.
Authors: Ernest V Groman; Meiheng Yang; Christopher P Reinhardt; James S Weinberg; Dennis E Vaccaro Journal: J Cardiovasc Transl Res Date: 2009-01-14 Impact factor: 4.132
Authors: Sara Prijic; Janez Scancar; Rok Romih; Maja Cemazar; Vladimir B Bregar; Andrej Znidarsic; Gregor Sersa Journal: J Membr Biol Date: 2010-07-03 Impact factor: 1.843