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 erythropoietin (pVRmEpo) to BALB/c mice by gene gun. Whereas intramuscular injection elicits a rise in hematocrit persisting >8 months, intradermal delivery triggers the dose-dependent secretion of biologically active erythropoietin (Epo) for approximately 1 month. Repeated administration of pVRmEpo by gene gun elicits a stable increase in hematocrit. The source of the Epo produced following gene gun delivery was analyzed by periodically grafting the site of injection onto naive recipients. Results indicate that both stationary cells (presumably keratinocytes) and migratory (presumably dendritic) cells were transfected and secreted biologically active Epo in vivo. Gene gun administration of plasmid DNA appears to be safe, and provides an additional strategy for achieving the regulated secretion of an exogenous gene product.
Klinman
D M
DM
Retroviral Immunology Section, Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA. klinman@A1.cber.fda.gov
Conover
J
J
Leiden
J M
JM
Rosenberg
A S
AS
Sechler
J M
JM
D000740:Anemia / Q000628:therapy; D000818:Animals; D001483:Base Sequence; D019470:Biolistics / Q000009:adverse effects / Q000592:standards; D004247:DNA / Q000008:administration & dosage*; D017931:DNA Primers; D004921:Erythropoietin / Q000235:genetics*; D005260:Female; D006400:Hematocrit; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000008:administration & dosage*
D017931:DNA Primers; D004921:Erythropoietin; D004247:DNA