Improvement of mouse beta-thalassemia by electrotransfer of erythropoietin cDNA

Exp Hematol. 2001 Mar;29(3):295-300. doi: 10.1016/s0301-472x(00)00679-2.


Objective: A new intramuscular DNA electrotransfer method for erythropoietin (EPO) expression was evaluated in the natural mouse model of human beta-thalassemia (Hbb-thal1) in terms of its ability to reverse the anemia and improve the thalassemic features of erythrocytes.

Materials and methods: Intramuscular injection of small amounts of a plasmid encoding mouse EPO, immediately followed by controlled electric pulses, was used.

Results: This procedure induced very high hematocrit levels in beta-thalassemic mice compared to nonelectrotransferred mice. The hematocrit increase was dose dependent, still increased 4 months after injection of plasmid DNA, and associated with a high transgenic EPO blood level in all mice (up to 2500 mU/mL of plasma). EPO gene electrotransfer not only led to a long-lasting and dose-dependent increase in the hematocrit but also to a 100% increase in the lifespan of erythrocytes of thalassemic mice. This was related to a nearly complete reestablishment of alpha/beta globin chain balance, as demonstrated by a marked decrease in unpaired alpha globin chain. Eight months after the first electrotransfer of pCMV-mEPO plasmid, reinjection of the same construct raised the hematocrit to a level close to that observed following the first electrotransfer.

Conclusion: This is the first description of the use of plasmid DNA to achieve long-term improvement in a mouse model of a human genetic disorder.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytomegalovirus / genetics
  • DNA, Recombinant / administration & dosage*
  • DNA, Recombinant / genetics
  • Disease Models, Animal
  • Electroporation*
  • Erythropoietin / biosynthesis
  • Erythropoietin / genetics*
  • Erythropoietin / physiology
  • Female
  • Gene Deletion
  • Genetic Therapy*
  • Genetic Vectors / administration & dosage
  • Globins / deficiency
  • Globins / genetics
  • Hematocrit
  • Injections, Intramuscular
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Promoter Regions, Genetic
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / physiology
  • Transgenes
  • beta-Thalassemia / genetics
  • beta-Thalassemia / therapy*


  • DNA, Recombinant
  • Recombinant Fusion Proteins
  • Erythropoietin
  • Globins