TECHNOLOGYElectroporation
VGX International's DNA vaccine uses the Electroporation DNA delivery technology to deliver DNA vaccines into the cell membrane.  The primary limitation with 1st generation vaccines was the inefficiency of the delivery system- naked DNA was not effectively taken up by muscle cells to express antigens. To overcome this hurdle, VGX Int'l has employed electroporation with the CELLECTRA® by administering a series of electric pulses into the DNA injected tissue, and it increases DNA transfection by opening cell membrane pores and immunogenicity by inciting localized inflammation.

Picture1. Process of DNA Vaccine Administration via Electroporation
① DNA vaccine injected into selected muscle using syringe and needle electrodes
② An electric field is formed when electrical pulses are applied
③ The electrical field creates temporary openings in the cell membrane
④ DNA vaccine is delivered in the cells

* Source: INOVIO Pharmaceuticals, Inc

Electroporation technology can increase cellular uptake of an agent by 1,000 times or more.
It was shown to increase levels of gene expression by 100 times or more compared to plasmid DNA alone.

Picture 2. Increase of Gene Expression. Preclinical testing in large animals such as pigs has shown that electroporation-based DNA delivery technology increased neutralizing antibody production more than 100 times.

* Source: INOVIO Pharmaceuticals, Inc
The purpose of DNA vaccination is to elicit immune responses for specific targeting antigens and through that the body will be able to overcome diseases that have similar virus antigens. The two graphs below are data that confirmed how much humoral immune responses and cellular immune responses (T-cell) have been increased via the electroporation technology; and the effectiveness of electroporation can be seen.

Picture 3. Increased Immune Response. Pre-clinical testing in large animals such as monkeys have shown that electroporation-based DNA delivery technology increased neutralizing antibody production more than 100 times.

* Source: INOVIO Pharmaceuticals, Inc

Picture 4. . Increase in Immune Response. Pre-clinical testing in large animal models such as monkeys have shown that the electroporation-based DNA delivery technology increased the breadth and magnitude of T-cell production from a multi-antigen DNA vaccine against HIV. It showed over 200 times increase in potency of the DNA vaccine, which match or exceed those achieved using viral or lipid delivery methods, but without side effects that hinder the approaches

* Source: INOVIO Pharmaceuticals, Inc

There are several delivery methods developed to deliver DNA vaccines such as viral vector, liposome of lipid vectors, gene gun or particle gun, and electroporation.  [Refer to Tabel 1]

Table 1. Comparison with Other Delivery Methods

Delivery Methods Carrier Issues Efficacy Cost
Virus Mutations
immune responses
infection symptoms
+++++ $$$$$
Lipid Toxicity ++ $$
Particle Gun Manufacturabillty ++ $$
Naked DNA Nocarrier + $
Naked DNA &
Electroporation
Nocarrier ++++ $$

Virus vectors (carriers) use the virus to carry genes such as a DNA vaccine to the target cell. It is an extremely effective method that is broadly being used and tested. However, it may induce unwanted immune responses ‘against themselves, making the patient resistant to subsequent vaccinations using the same viral vector. Also, regulations are tight due to safety concerns, and the cost is extremely high.

Lipisome or lipid vectors are modified DNA vaccine carriers using the advantage of the lipid component which can easily cross the cell membrane. They also have the advantage of using the lipid component as an adjuvant, however, they are not as effective in delivering the DNA (ineffective than viral vectors), cost challenging, and has safety issues such as toxicity shown in vivo.

Gene gun or particle gun delivery method uses the DNA-vaccine-coated gold particles into the patient’s skin.  This has been used for a long time and could be safely delivered as it uses a dry DNA, however, there are manufacturing challenges and since only a limited quantity could be delivered to the skin, it is only effective in diseases that target specific areas such as solid cancers.

Electroporation (EP) is a very safe delivery method compared to other methods like the viral or lipid vector, since its pure DNA is delivered via electroporation. Also, it is as effective as the viral vector, thus, it is attracting attention and endorsements from scientists.

Picture 5. Comparison data between Electroporation and the Viral Vector. Electroporation delivery method compared to the Adenovirus vector was shown to increase 10 times of SIV DNA vaccine cell expression in monkeys

* Source: INOVIO Pharmaceuticals, Inc