Piezoelectric permeabilization of mammalian dermal tissue for in vivo DNA delivery leads to enhanced protein expression and increased immunogenicity.
Electropermeabilization of mammalian cells is a technique that has been used for the delivery of therapeutics, such as DNA plasmids or DNA vaccines. Typically, delivery via electropermeabilization occurs through injection of the substance into the tissue of interest followed by the insertion of electrodes at the site and the application of brief electrical pulses. Here we detail a novel and innovative contactless electropermeabilization method to deliver DNA plasmids to dermal tissue in vivo. This process has the advantage of eliminating the insertion of additional needles that serve as electrodes to facilitate the application of electric pulses in conventional electroporation processes. Plasmid encoding GFP was injected into guinea pig skin and pulsed with the novel contactless electropermeabilization method. Three days following treatment, robust GFP expression was observed on the skin of pulsed animals. Strong humoral immune responses were also achieved when a DNA vaccine expressing the influenza antigen NP was delivered and pulsed using the novel device in comparison to naked injection alone. This delivery method has the advantage of being contactless and suggests that gene transfer via this mode warrants further development.
Inovio Pharmaceuticals, Inc., San Diego, CA USA.
Kate E
KE
Broderick
Thomas
T
Kardos
Jay R
JR
McCoy
Michael P
MP
Fons
Stephen
S
Kemmerrer
Niranjan Y
NY
Sardesai
D000818:Animals; D000941:Antigens / Q000096:biosynthesis* / Q000235:genetics; D020405:Dermis / Q000502:physiology*; D018274:Electroporation / Q000379:methods*; D015870:Gene Expression; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D006168:Guinea Pigs; D010539:Permeability; D010957:Plasmids; D014611:Vaccination / Q000379:methods*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000941:Antigens; D019444:Vaccines, DNA; D049452:Green Fluorescent Proteins