Potent Intradermal Gene Expression of Naked Plasmid DNA in Pig Skin Following Pyro-drive Jet Injection

Abstract

Intradermal administration of naked DNA with a conventional needle syringe is a simple and inexpensive method to expose an encoded antigen to the dermal immune system. We aimed to enhance intradermal gene expression with a pyro-drive jet injector using pig skin, which is similar in structure and biomechanical properties to human skin. When Cy3-labeled plasmid (pCy3) was applied to pig skin with the jet injector, pCy3 was distributed preferentially in the intradermal tissue. Precise localization analysis revealed that pCy3 was also detected in the intracellular nucleus, and the frequency was substantially higher with the jet injector than with a needle syringe. When a luciferase expression plasmid (pLuc) was injected transdermally, the luciferase activity was 380-fold higher with the jet injector than with a needle syringe. Furthermore, immunohistochemistry analysis showed that the epidermis was positive for luciferase protein expression. These data indicate that the jet injector facilitates stable intradermal administration, resulting in more efficient gene expression compared to that with conventional syringe methods. Thus, intradermal administration of an antigen-expression plasmid with the pyro-drive jet injector may provide a clinically viable method for future gene therapy.