Efficient and regulated erythropoietin production by naked DNA injection and muscle electroporation

We show that an electric treatment in the form of high-frequency, low-volta ge electric pulses can increase more than 100-fold the production and secre tion of a recombinant protein from mouse skeletal muscle. Therapeutical ery thopoietin (EPO) levels were achieved in mice with a single injection of as little as 1 mu g 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 hemat ocrit levels. Tissue damage after stimulation was transient. The method des cribed thus provides a potentially safe and low-cost treatment for serum pr otein deficiencies.