title: Efficient and regulated erythropoietin production by naked DNA injection and muscle electroporation.
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.
authors.affiliation: Istituto di Ricerche di Biologia Molecolare P. Angeletti, 00040 Pomezia, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Rizzuto
authors.forename: M
authors.initials: M
authors.lastname: Cappelletti
authors.forename: D
authors.initials: D
authors.lastname: Maione
authors.forename: R
authors.initials: R
authors.lastname: Savino
authors.forename: D
authors.initials: D
authors.lastname: Lazzaro
authors.forename: P
authors.initials: P
authors.lastname: Costa
authors.forename: I
authors.initials: I
authors.lastname: Mathiesen
authors.forename: R
authors.initials: R
authors.lastname: Cortese
authors.forename: G
authors.initials: G
authors.lastname: Ciliberto
authors.forename: R
authors.initials: R
authors.lastname: Laufer
authors.forename: N
authors.initials: N
authors.lastname: La Monica
authors.forename: E
authors.initials: E
authors.lastname: Fattori
mesh_terms: 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
chemical_list: D020121:5' Untranslated Regions; D011994:Recombinant Proteins; D004921:Erythropoietin