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-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.
Rizzuto
G
G
Istituto di Ricerche di Biologia Molecolare P. Angeletti, 00040 Pomezia, Rome, Italy.
Cappelletti
M
M
Maione
D
D
Savino
R
R
Lazzaro
D
D
Costa
P
P
Mathiesen
I
I
Cortese
R
R
Ciliberto
G
G
Laufer
R
R
La Monica
N
N
Fattori
E
E
D020121:5' Untranslated Regions / Q000235:genetics; D000818:Animals; D003587:Cytomegalovirus / Q000235:genetics; D004558:Electric Stimulation; D018274:Electroporation / Q000379:methods; D004921:Erythropoietin / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology*; D010957:Plasmids; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000096:biosynthesis; D012680:Sensitivity and Specificity; D013997:Time Factors
D020121:5' Untranslated Regions; D011994:Recombinant Proteins; D004921:Erythropoietin