title: Gene electrotransfer results in a high-level transduction of rat skeletal muscle and corrects anemia of renal failure.
abstract: We have investigated the efficacy of a gene transfer strategy based on plasmid DNA electroinjection for the correction of anemia associated with renal failure. An expression plasmid encoding the rat erythropoietin (EPO) cDNA under the control of the CMV promoter as constructed and utilized for this work. Electroinjection of pCMV/rEPO in different rat muscles yielded sustained and long-term EPO production and secretion. The muscle-produced EPO corrected the anemia in five of six nephrectomized rats, used as a model of renal failure. The efficiency of muscle transduction was comparable in rats and mice injected with equivalent amounts of DNA per kilogram of body weight. These results demonstrate that gene electrotransfer can be applied to produce therapeutically significant levels of erythropoietin in chronic renal failure.
authors.affiliation: Istituto di Richerche 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: C
authors.initials: C
authors.lastname: Mennuni
authors.forename: M
authors.initials: M
authors.lastname: Wiznerowicz
authors.forename: A
authors.initials: A
authors.lastname: DeMartis
authors.forename: D
authors.initials: D
authors.lastname: Maione
authors.forename: G
authors.initials: G
authors.lastname: Ciliberto
authors.forename: N
authors.initials: N
authors.lastname: La Monica
authors.forename: E
authors.initials: E
authors.lastname: Fattori
mesh_terms: D000740:Anemia / Q000209:etiology / Q000628:therapy*; D000818:Animals; D003587:Cytomegalovirus / Q000235:genetics; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D006400:Hematocrit; D007267:Injections / Q000379:methods; D007676:Kidney Failure, Chronic / Q000150:complications*; D051379:Mice; D008807:Mice, Inbred BALB C; D018482:Muscle, Skeletal / Q000502:physiology*; D009392:Nephrectomy; D010957:Plasmids / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D014161:Transduction, Genetic
chemical_list: D004921:Erythropoietin