Gene electrotransfer into skin using noninvasive multi-electrode array for vaccination and wound healing

Bioelectrochemistry. 2017 Apr:114:33-41. doi: 10.1016/j.bioelechem.2016.12.002. Epub 2016 Dec 10.

Abstract

Skin is an attractive target for gene electrotransfer due to its easy accessibility and its interesting immune properties. Since electrodes are often invasive and frequently induce discomfort during pulse application, there is a fundamental need for non-invasive electrodes for skin delivery. We developed circular pin non-invasive multi-electrode array (MEA), suitable for different clinical applications. MEA was first employed to deliver a luciferase reporter gene. Then, it was used to deliver a DNA vaccine coding for ovalbumin or a plasmid encoding hCAP-18/LL-37 for promoting wound healing. The results demonstrated a strong gene expression and an efficient delivery of both, DNA vaccine and wound healing agent, dependent on the pulses applied. The use of MEA to deliver the ovalbumin plasmid demonstrated a strong immune response, as evidenced by the presence of antibodies in sera, the IFN-gamma response and the delayed tumor growth when the mice were subsequently challenged with B16-OVA cells. The delivery of a plasmid encoding hCAP-18/LL-37 significantly accelerated wound closure. The easy applicability and non-invasiveness of MEA make it suitable for various clinical applications that require gene electrotransfer to skin. Specifically, by adapting electric pulses to the expected action of a transgene, non-invasive MEA can be employed either for vaccination or for wound healing.

Keywords: Electroporation; Multi-electrode array; Plasmid DNA; Skin; Vaccination; Wound healing.

MeSH terms

  • Animals
  • Antimicrobial Cationic Peptides / genetics
  • Cathelicidins
  • Cell Line, Tumor
  • Cytokines / biosynthesis
  • Electrodes
  • Gene Transfer Techniques / instrumentation*
  • Genes, Reporter / genetics
  • Humans
  • Immunoglobulin G / biosynthesis
  • Luciferases / genetics
  • Mice
  • Plasmids / genetics
  • Skin / metabolism*
  • Spleen / immunology
  • Spleen / metabolism
  • Vaccination / instrumentation*
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology
  • Wound Healing*

Substances

  • Antimicrobial Cationic Peptides
  • Cytokines
  • Immunoglobulin G
  • Vaccines, DNA
  • Luciferases
  • Cathelicidins