Safe and effective regulation of hematocrit by gene gun administration of an erythropoietin-encoding DNA plasmid

This work examines the effect of delivering a DNA plasmid encoding murine e rythropoietin (pVRmEpo) to BALB/c mice by gene gun, Whereas intramuscular i njection elicits a rise in hematocrit persisting >8 months, intradermal del ivery triggers the dose-dependent secretion of biologically active erythrop oietin (Epo) for similar to 1 month. Repeated administration of pVRmEpo by gene gun elicits a stable increase in hematocrit. The source of the Epo pro duced following gene gun delivery was analyzed by periodically grafting the site of injection onto naive recipients. Results indicate that both statio nary cells (presumably keratinocytes) and migratory (presumably dendritic) cells were transfected and secreted biologically active Epo in vivo. Gene g un administration of plasmid DNA appears to be safe, and provides an additi onal strategy for achieving the regulated secretion of an exogenous gene pr oduct.