title: Electroporation-mediated gene transfer directly to the swine heart.
abstract: In vivo gene transfer to the ischemic heart via electroporation holds promise as a potential therapeutic approach for the treatment of heart disease. In the current study, we investigated the use of in vivo electroporation for gene transfer using three different penetrating electrodes and one non-penetrating electrode. The hearts of adult male swine were exposed through a sternotomy. Eight electric pulses synchronized to the rising phase of the R wave of the electrocardiogram were administered at varying pulse widths and field strengths following an injection of either a plasmid encoding luciferase or one encoding green fluorescent protein. Four sites on the anterior wall of the left ventricle were treated. Animals were killed 48 h after injection and electroporation and gene expression was determined. Results were compared with sites in the heart that received plasmid injection but no electric pulses or were not treated. Gene expression was higher in all electroporated sites when compared with injection only sites demonstrating the robustness of this approach. Our results provide evidence that in vivo electroporation can be a safe and effective non-viral method for delivering genes to the heart, in vivo.
authors.affiliation: Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA 23508, USA.
authors.forename: B
authors.initials: B
authors.lastname: Hargrave
authors.forename: H
authors.initials: H
authors.lastname: Downey
authors.forename: R
authors.initials: R
authors.lastname: Strange
authors.forename: L
authors.initials: L
authors.lastname: Murray
authors.forename: C
authors.initials: C
authors.lastname: Cinnamond
authors.forename: C
authors.initials: C
authors.lastname: Lundberg
authors.forename: A
authors.initials: A
authors.lastname: Israel
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Chen
authors.forename: W
authors.initials: W
authors.lastname: Marshall
authors.forename: R
authors.initials: R
authors.lastname: Heller
mesh_terms: D000818:Animals; D004566:Electrodes; D018274:Electroporation / Q000295:instrumentation / Q000379:methods*; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006352:Heart Ventricles / Q000378:metabolism*; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D013552:Swine
chemical_list: D049452:Green Fluorescent Proteins; D008156:Luciferases