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PMID: 10339602 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 96 ·No. 11 ·1999-05-25 ·Pages 6417-22

Rizzuto G, Cappelletti M, Maione D, Savino R, Lazzaro D, Costa P, Mathiesen I, Cortese R, Ciliberto G, Laufer R, La Monica N, Fattori E

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.

MeSH Terms
5' Untranslated Regions/genetics Animals Cytomegalovirus/genetics Electric Stimulation Electroporation/methods Erythropoietin/biosynthesis,blood,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,physiology Plasmids Promoter Regions, Genetic Recombinant Proteins/biosynthesis Sensitivity and Specificity Time Factors
Chemicals
5' Untranslated Regions Recombinant Proteins Erythropoietin
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Rizzuto G
Istituto di Ricerche di Biologia Molecolare P. Angeletti, 00040 Pomezia, Rome, Italy.
Cappelletti M
Maione D
Savino R
Lazzaro D
Costa P
Mathiesen I
Cortese R
Ciliberto G
Laufer R
La Monica N
Fattori E
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.96.11.6417
Published
1999-05-25
Pages
6417-22
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC26896
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.96.11.6417 PMC Full Text View journal details
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