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Electroporation delivery system wins biothreat contract

By Katrina Megget, 07-Aug-2007

Related topics: Materials & Formulation, Drug delivery systems

San Diego-based Ichor Medical Systems has been awarded a more than $2.3m contract to develop an electroporation DNA vaccine delivery system for anthrax and plague in the event of bioterrorism.

The two-year contract, awarded by the US Department of Defense's Defense Threat Reduction Agency (DTRA), would explore the potential of electroporation-based drug delivery systems to increase the effectiveness of biodefense-related DNA vaccine candidates.

The anthrax and plague vaccine candidates have already been developed by the Biological Defense Research Directorate (BDRD) of the Naval Medical Research Centre (NMRC) in Rockville, Maryland.

The administration of the vaccines would use Ichor's proprietary TriGrid electroporation delivery system.

Electroporation, where a brief electrical pulse is used to create temporary openings in cell membranes through which substances can enter the cell, has been used in research laboratories for about 20 years.

In the last few years, electroporation technology has been investigated and developed as a potential drug delivery system for, particularly, DNA vaccines, and it has been shown in studies that the technology can increase the uptake of agents by up to 1,000-fold compared to other methods of delivery.

"Ichor's TriGrid represent's a promising platform technology for the rapid deployment of vaccines against anthrax, plague, and other biothreat agents," Ichor director of infectious disease programs Dr Alain Luxembourg said in a statement.

"We are excited by the possibility to assess Ichor's technology for the delivery of advanced DNA vaccine designs conceived by the Navy."

Ichor's system is the first integrated, fully automated clinical electroporation system which allows the delivery of DNA encoding vaccines and other gene-based therapies in one step to endogenously produce protein from the patient's own muscle.

Other systems in use are based on more than one step where the DNA must be injected first and then electrode needles are implanted manually into the tissue for activation.

Ichor's TriGrid system combines the syringe needle and four electrodes in the same device.

The small hand-held device works by being held against the patient's upper arm. When a button is pushed the device deploys the needle and electrodes at a fixed depth and location and delivers the DNA drug and the electrical field to each patient in a consistent manner.

The electrodes are arranged in a diamond shape around the central syringe and enter a space in the muscle tissue that is smaller than one cubic centimeter.

The one-step method is considered by Ichor to be more effective than the two-step method which can create more variable results and reduced transfection rates.

"This is an advantageous platform technology because the DNA to be delivered can be changed rapidly and relatively inexpensively," Ichor director of business development May de la Alas told US-PharmaTechnologist.com.

"The DNA may need to be changed as a result of viral mutation - for example the current concerns with the H5N1 avian flu virus and if it should mutate. It may also need to be changed because a new threat has emerged. For example, the SARS of yesterday and the anthrax and avian flu of today may be something totally different tomorrow. Also, our enemies may be plotting to use a combination of biological weapons. The TriGrid platform can deliver any combination of vaccines to attack these threats."

Ichor is involved in a number of pre-clinical and clinical studies exploring the potential treatment of diseases including atherosclerosis, avian flu, hepatitis B, HIV, melanoma, and multiple sclerosis.

In March, the biotech company was awarded a $900,000 contract buy the US Department of Defense to assist the US Army in the development of a DNA vaccine for equine encephalitis.

Inovio Biomedical is another company exploring electroporation as a DNA plasmid vaccine delivery technique and was awarded $1.1m by the US Department of Defense to use the company's MedPulser to develop enhanced delivery methods for vaccines against bio-agents.

MedPulser, which is a two-step system, has also been involved in trials for a prostate cancer vaccine, the delivery of interleukin-12 and interleukin-2 for malignant melanomas, and a DNA vaccine delivered intramuscularly for breast, ovarian and colorectal cancers expressing HER2 and/or carcinoembryonic antigen.

The technology won a significant endorsement last November when Wyeth Pharmaceuticals agreed to pay up to $64.5m for a non-exclusive license to the MedPulser DNA Delivery System for intramuscular applications of certain therapeutic DNA vaccines.

Amaxa has also developed a transfection technique based on electroporation used with primary cells and cell lines.

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