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- W2098088508 abstract "Adverse effects (death and leukemogenesis) from viral vector-mediated gene therapy have renewed interest in plasmids as safer, more scalable, simple, and cost-effective vectors. Electroporation and hydrodynamic delivery are two techniques that improve the efficiency of plasmid-mediated gene transfer. The liver is a good tissue platform for targeted transfer of therapeutically relevant genes for correction of metabolic disorders, for example, hemophilia A. However, in vivo electroporation of liver has not yet been shown to achieve therapeutic efficacy of systemically active, secreted transgenic proteins. We have investigated the effect of field strength, pulse duration, pulse number, electrical waveforms, electrode contact area, plasmid administration routes, and injection technique on the efficiency of in vivo electrotransfer of naked plasmid to liver. Plasmid injection into a systemic vein was superior to intrahepatic injection. Unlike in vivo muscle electroporation, high-voltage pulses and microsecond pulses offered no advantage. Optimal electroporation conditions were 8–10 uni- or bipolar pulses of 20 msec, each at 250 V/cm. Using a nonhydrodynamic technique that greatly enhanced electrotransfer efficiency with minimal tissue injury, we demonstrate for the first time that liverdirected in vivo electroporation of factor VIII cDNA achieved significant phenotypic correction in hemophilic mice." @default.
- W2098088508 created "2016-06-24" @default.
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- W2098088508 date "2006-03-01" @default.
- W2098088508 modified "2023-10-15" @default.
- W2098088508 title "<i>In Vivo</i> Liver Electroporation: Optimization and Demonstration of Therapeutic Efficacy" @default.
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- W2098088508 doi "https://doi.org/10.1089/hum.2006.17.362" @default.
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