Contactless magneto-permeabilization for intracellular plasmid DNA delivery in-vivo.

Electroporation, an attractive process for delivering DNA and other molecules into target cells in vivo and in vitro is limited by the necessity of electrodes that need to be in contact with the subject or object to be electroporated. We have used magnetic fields, which do not require material contact with the subject, to temporarily permeabilize cells in guinea pig skin in vivo to enhance uptake and expression of GFP plasmid DNA. The results show for the first time that magnetic fields can trigger a process likely similar to electroporation.

Tolerability of two sequential electroporation treatments using MedPulser DNA delivery system (DDS) in healthy adults.

Immunotherapy against infectious agents and malignant tumors requires efficient priming of effector cells through direct expression and/or efficient cross-presentation of antigens by antigen-presenting cells. Electroporation is a new procedure aimed at transiently increasing cell membrane permeability and direct delivery of antigen or antigen-encoding nucleic acids inside targeted cells. We evaluated the tolerability including compliance with repeated electroporation treatments using MedPulser DDS in 24 healthy adults.

A therapeutic SIV DNA vaccine elicits T-cell immune responses, but no sustained control of viremia in SIVmac239-infected rhesus macaques.

The immunologic and virologic outcome of therapeutic DNA-vaccines administered during antiretroviral therapy (ART) using electroporation with or without (interleukin) IL-2 treatment was evaluated in the SIVmac239/macaque model. Rhesus macaques inoculated with pathogenic SIVmac239 were treated with ART [(R(-9-(2-phosphonomethoxypropyl) adenine) (PMPA), FTC, Zerit] from weeks 13 to 41 postinfection (wpi). Group 1 (n = 7) received ART only, groups 2 and 3 (each n = 6) additionally received SIVmac239-derived gp140Env, GagPol, and TatRevNef plasmids by in vivo electroporation at 22, 26, 30, and 34 wpi, and group 3 also IL-2 for 14 days after each vaccination.

Taking electroporation-based delivery of DNA vaccination into humans: a generic clinical protocol.

We are presently aware of two early-phase DNA vaccine clinical trials in humans using electroporation-enhanced vaccine delivery. Moreover, two phase I immunogenetherapy studies are in progress and several tolerability studies have been performed on healthy volunteers. We have used knowledge from these studies to compose a template for clinical protocols involving electroporation-mediated gene delivery.

Applicator and electrode design for in vivo DNA delivery by electroporation.

As in vivo electroporation advances from the preclinical phase to clinical studies and eventually to routine medical practice, the design of electroporation devices becomes increasingly important. Achieving safety and efficacy levels that meet regulatory requirements, as well as user and patient friendliness, are major design considerations. In addition, the devices will have to be economical to manufacture.