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

Proc Natl Acad Sci U S A. 1999 May 25;96(11):6417-22. doi: 10.1073/pnas.96.11.6417.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions / genetics
  • Animals
  • Cytomegalovirus / genetics
  • Electric Stimulation
  • Electroporation / methods
  • Erythropoietin / biosynthesis
  • Erythropoietin / blood
  • Erythropoietin / genetics*
  • Female
  • Gene Expression Regulation
  • Gene Transfer Techniques*
  • Kinetics
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / physiology*
  • Plasmids
  • Promoter Regions, Genetic
  • Recombinant Proteins / biosynthesis
  • Sensitivity and Specificity
  • Time Factors

Substances

  • 5' Untranslated Regions
  • Recombinant Proteins
  • Erythropoietin