Genetronics vice president Dietmar Rabussay, PhD, outlines the history of electroporation. "The phenomenon was really seen the first time in the 1970s. In the late 1980s, the first application of electroporation got drugs in vivo into tumors in rats. Two years later, the first human treatments were done in France." At the same time, Genetronics started to use this technology, primarily for delivering cancer drugs into tumors.

Since the early 1990s, Genetronics has been developing electroporation as a medical device for in vivo treatment of cancer, and has staked out an intellectual property position with more than 200 patents issued or pending. The device functions by the insertion of six needle probes into the tissue and the passing of an electrical current through tissue for several microseconds at a time. The presence of an electrical field induces a permeability change.

Genetronics succeeded in using this technology for the treatment of cancer. Pairing the pulsed electrical current with the drug bleomycin, the company reports being able to shrink as many as 100% of tumors in some studies. Merck now plans to use a modification of this method in an as-yet-unannounced DNA vaccine program.

Gene therapy and DNA vaccine development have been hindered by delivery problems. Early attempts focused on viruses as vectors, but many researchers are rejecting viral vectors and instead favor delivery of naked DNA as safer and more predictable. "The critical thing to understand is that we're not using any cellular uptake machinery to get the compound in," says Avtar Dhillon, MD, CEO of Genetronics. "We're not using carrier proteins or endocytotic mechanisms. Typically, there is no damage to the cell."

Genetronics executives look forward to the completion of clinical trials with MedPulser as a DNA vaccine delivery system and to developing new corporate partnerships. "We hope there will be broader recognition of electroporation as a tool, not only for delivery of a gene, but to enhance immune responses," says Dhillon.

By Catherine Shaffer