A novel electroporation device for gene delivery in large animals and humans.
Intramuscular injection of plasmid DNA followed by electrical stimulation (electroporation) is an efficient method for achieving therapeutic levels of encoded proteins or eliciting efficient immune responses in smaller animals such as mice and rats. Electroporation in larger animals and humans poses new technical challenges, the main difficulty being to maintain efficacy while limiting invasiveness and pain. Here we present data using a new device for combined injection and electroporation in large animals and humans. The device injects DNA through two needles during insertion into the muscle and thus distributes the injection volume along the needles which also serve as electrodes. Since the electrical field is strongest close to the needle-electrode, a near perfect match between the DNA and the electric field is achieved. We show that using moderate amounts of DNA: (1) muscle tissue is transfected along the entire length of the needle path, (2) the efficacy is higher compared to when the DNA is injected between the electrodes, (3) level of protein expression can be tightly controlled by the number of treatments, and (4) efficient immunization is achieved.
Tjelle
Torunn Elisabeth
TE
Inovio AS, Forskningsveien 2a, Box 180-Vindern, 0319 Oslo, Norway. tjelle@inovio.com
Salte
Ragnar
R
Mathiesen
Iacob
I
Kjeken
Rune
R
D000818:Animals; D000917:Antibody Formation; D004566:Electrodes; D018274:Electroporation / Q000295:instrumentation*; D004867:Equipment Design; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D051379:Mice; D009339:Needles; D051381:Rats; D001616:beta-Galactosidase / Q000235:genetics
D049452:Green Fluorescent Proteins; D001616:beta-Galactosidase