Electroporation-mediated delivery of a naked DNA plasmid expressing VEGF to the porcine heart enhances protein expression.
Gene therapy is an attractive method for the treatment of cardiovascular disease. However, using current strategies, induction of gene expression at therapeutic levels is often inefficient. In this study, we show a novel electroporation (EP) method to enhance the delivery of a plasmid expressing an angiogenic growth factor (vascular endothelial growth factor, VEGF), which is a molecule previously documented to stimulate revascularization in coronary artery disease. DNA expression plasmids were delivered in vivo to the porcine heart with or without coadministered EP to determine the potential effect of electrically mediated delivery. The results showed that plasmid delivery through EP significantly increased cardiac expression of VEGF compared with injection of plasmid alone. This is the first report showing successful intracardiac delivery, through in vivo EP, of a protein expressing plasmid in a large animal.
Marshall
W G
WG
Department of Surgery, University of South Florida, Tampa, FL, USA.
Boone
B A
BA
Burgos
J D
JD
Gografe
S I
SI
Baldwin
M K
MK
Danielson
M L
ML
Larson
M J
MJ
Caretto
D R
DR
Cruz
Y
Y
Ferraro
B
B
Heller
L C
LC
Ugen
K E
KE
Jaroszeski
M J
MJ
Heller
R
R
D000818:Animals; D003324:Coronary Artery Disease / Q000628:therapy*; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D018274:Electroporation / Q000379:methods*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006321:Heart; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D014176:Protein Biosynthesis / Q000235:genetics; D013552:Swine; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics*
D042461:Vascular Endothelial Growth Factor A; D004247:DNA