Proceedings of the National Academy of Sciences · 1999 · 325 citations · 35 references
MedicineBiotechnologyHematologyGene DeliveryGene TherapyRecombinant Dna TechnologyAnemiaBioelectronic MedicineHematocrit RegulationIn Vivo Gene TherapyRecombinant Protein ExpressionRecombinant Protein ProductionElectroporationElectroporation-mediated DeliveryErythropoiesis-stimulating TherapyErythropoietin RegulationGene ElectrotransferPulsed Electric Field TreatmentTetracycline-inducible Gene ExpressionTissue Electroporation
We show that an electric treatment in the form of high-frequency, low-voltage electric pulses can increase more than 100-fold the production and secretion of a recombinant protein from mouse skeletal muscle. Therapeutical erythopoietin (EPO) levels were achieved in mice with a single injection of as little as 1 microgram of plasmid DNA, and the increase in hematocrit after EPO production was stable and long-lasting. Pharmacological regulation through a tetracycline-inducible promoter allowed regulation of serum EPO and hematocrit levels. Tissue damage after stimulation was transient. The method described thus provides a potentially safe and low-cost treatment for serum protein deficiencies.
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Direct Gene Transfer into Mouse Muscle in Vivo
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Transcriptional Activation by Tetracyclines in Mammalian Cells
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Gene transfer into muscle by electroporation in vivo
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