Long-term production of erythropoietin after electroporation-mediated transfer of plasmid DNA into the muscles of normal and uremic rats

Citation
H. Maruyama et al., Long-term production of erythropoietin after electroporation-mediated transfer of plasmid DNA into the muscles of normal and uremic rats, GENE THER, 8(6), 2001, pp. 461-468
Citations number
33
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
GENE THERAPY
ISSN journal
0969-7128 → ACNP
Volume
8
Issue
6
Year of publication
2001
Pages
461 - 468
Database
ISI
SICI code
0969-7128(200103)8:6<461:LPOEAE>2.0.ZU;2-U
Abstract
The anemia associated with chronic renal failure is one of the best target diseases for erythropoietin (Epo) gene transfer. We previously reported a s hort-term (1 month) study of continuous rat Epo delivery by muscle-targeted gene transfer of plasmid DNA expressing rat Epo (pCAGGS-Epo) using in vivo electroporation in normal rats. Here, we performed a long-term pharmacokin etic study of continuous Epo delivery by this method in normal rats and ure mic five-sixths nephrectomized rats. In normal rats, Epo gene expression an d sufficient erythropoiesis occurred with Epo gene transfer in a dose-depen dent manner, and persisted for at least 11 weeks. Repeated administration o f the plasmid DNA effectively produced erythropoiesis. Similar erythropoies is was observed in the uremic rats, and persisted for more than 15 weeks. B oth normal and uremic rats showed a significant decrease in platelet count. Moreover, the uremic rats showed Epo-induced hypertension, which is the ma jor side-effect of recombinant human Epo. These results demonstrate that mu scle-targeted pCAGGS-Epo transfer by in vivo electroporation is a useful pr ocedure for the long-term continuous delivery of Epo in both normal and ure mic rats.