Gene electrotransfer results in a high-level transduction of rat skeletal muscle and corrects anemia of renal failure

We have investigated the efficacy of a gene transfer strategy based on plas mid 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 sustai ned and long-term EPO production and secretion. The muscle-produced EPO cor rected the anemia in five of six nephrectomized rats, used as a model of re nal failure. The efficiency of muscle transduction was comparable in rats a nd mice injected with equivalent amounts of DNA per kilogram of body weight . These results demonstrate that gene electrotransfer can be applied to pro duce therapeutically significant levels of erythropoietin in chronic renal failure.