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

Gabriella Rizzuto, Manuela Cappelletti, Domenico Maione, Rocco Savino, Domenico Lazzaro, Patrizia Costa, Iacob Mathiesen, Riccardo Cortese, Gennaro Ciliberto, Ralph Laufer,

Proceedings of the National Academy of Sciences · 1999 · 325 citations · 35 references

Concepts

Abstract

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.

References

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