How Electroporation Works

The phenomenon of electroporation

In the 1970s, scientists discovered that applying electrical pulses to a cell (in a lab situation) enabled dramatically increased uptake of a biological material into the cell. This phenomenon, called electroporation, has since been documented by thousands of scientific papers (examples). While widely used in research laboratories, it wasn't until the 1990s that the first research was undertaken to investigate potential direct applications of electroporation to humans in vivo.

Inovio Pharmaceuticals, through its predecessor, Genetronics Biomedical Inc., was a pioneer in advancing the understanding and practical applications of electroporation for basic biological research purposes. Electroporation products the company developed for research applications (divested to Harvard Biosciences in 2002) are available today under the BTX brand from multiple vendors.

Today, Inovio commands a dominant position in intellectual property relating to human applications of electroporation. Inovio research has shown the potential utility of electroporation for human applications including oncology, gene therapy (including DNA-based immunotherapies and vaccines), cosmetic, vascular, transdermal, plant and ex vivo applications.

In all of these applications, the purpose of electroporation is to assist the uptake of useful molecules such as a DNA vaccine into a cell. The biological material is injected into or applied to the surface of the target tissue and followed by the application of brief, controlled electrical pulses directed to that tissue. As shown in the pictures below, electroporation's millisecond electrical pulses temporarily create enhanced permeability of pores in the cell membrane. After a short period of time the pores reseal, leaving the cells undamaged. During the period that these pores exist, a significant quantity of the previously injected biomolecules are taken up and then trapped in the cell, enabling them to then perform their intended function.

How does the electroporation process work?

The following illustration depicts the process of administering a DNA vaccine using electroporation:

Inovio's electroporation technology can increase the cellular uptake (also termed transfection) of an agent by 1,000 times or more. When used to deliver DNA vaccines, Inovio's systems can increase levels of gene expression (i.e. production of the coded protein) by 100 times or more compared to plasmid DNA delivered without other delivery enhancements.

Electroporation can significantly enhance the potency of DNA vaccines

Pre-clinical testing in large animal models has shown that Inovio's electroporation-based DNA delivery technology increased neutralizing antibody production more than 100 times.

Pre-clinical testing in large animal models has shown that Inovio's delivery technology increased the breadth and magnitude of T-cell production from a multi-antigen DNA vaccine against HIV. The test resulted in an increase in potency of the DNA vaccine by over 200 times. Such results would be considered to match or exceed those achieved using viral or lipid delivery methods, without the side effects that hamper these approaches.

Compelling first-in-man data using electroporation

Inovio partners have reported interim data from first-in-man phase I and phase I/II clinical trials. The University of Southampton reported a higher incidence and increased antibody response in patients treated using their experimental DNA vaccine for prostate cancer in conjunction with electroporation. Tripep reported an encouraging increase in T-cell responses from their DNA vaccine against hepatitis C virus delivered using Inovio's electroporation technology and concomitant reductions in HCV viral loads.

Inovio's DNA vaccine delivery technology

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