Inovio COVID-19 Vaccine Uses Electricity to Drive DNA Into Body Cells

Inovio COVID-19 Vaccine Uses Electricity to Drive DNA Into Body Cells


  • Inovio Pharmaceuticals has started Phase 1 testing of its experimental COVID-19 DNA vaccine in healthy volunteers.
  • The U.S. biotech firm has already produced enough of the vaccine to support Phase 1 (immune system reactivity and safety) and Phase 2 (efficacy) testing and plans to have one million doses ready for distribution by the end of 2020.
  • The experimental vaccinerequires a special device that uses electricity to drive DNA into cells of the body.

Inovio Pharmaceuticals headquartered in Pennsylvania, has just begun Phase 1 human clinical trials of its new DNA vaccine for COVID-19 (INO-4800).1Inovio’s experimental DNA vaccine uses an electrical device to deliver DNA directly into the cells of a person being vaccinated.2

The company’s Apr. 6, 2020 announcement of Phase 1 clinical trials stated:

“Preclinical data, which have been shared with global regulatory authorities and submitted as part of the IND, have shown promising immune response results across multiple animal models. Additional preclinical trials, including challenge studies, will continue in parallel with the Phase 1 clinical trial.”3

In the U.S., the development, testing and licensing process for an experimental vaccine generally takes 15-20 years to complete,45but there are calls to speed up the licensing process for COVID-19 vaccines.6Drug companies in the U.S. and other countries are racing to fast track their experimental COVID-19 vaccines to market within 12 to 18 months or even sooner.7If companies get an “emergency use” authorization from the Food and Drug Administration (FDA),8Inovio’s DNA vaccine could be among those vaccines ready by the fall of 2020 to be distributed to health care workers and other groups considered to be at “high risk” for COVID-19 infections or complications.

Funded by Gates, CEPI, DOD with Wistar & Other Partnerships

Inovio’s COVID-19 vaccine research has been funded by a $5M grant from the Bill and Melinda Gates Foundation and a $9M grant from the Norway-based Coalition for Epidemic Preparedness Innovations (CEPI).9Inovio also has a partnership with Philadelphia’s Wistar Institute and Beijing Advaccine Biotechnology Co. in Chinato develop the vaccine.1011

In addition, Inovio has a partnership with Ology Bioservices, Inc., headquartered in Florida. Ology and Inovio secured a $11.9M contract with the U.S. Department of Defenseto provide the experimental DNA coronavirus vaccine for upcoming clinical trials and potential manufacturing of the vaccine for military personnel in the future. In a Mar. 24 press release issued by Ology and Inovio, Douglas Bryce, Joint Program Executive Officer for Chemical, Biological, Radiological and Nuclear Defense, said:12

Given the current global health crisis, prophylaxis/vaccine developmentis critical to defend against the coronavirus disease 2019. We need several approaches to ensure we have a quick solution, and the medical countermeasures Advanced Development and Manufacturing Facility is poised to contribute to the race for a vaccine in coordination with our interagency partners like Health and Human Services, along with our partners in industry and academia.

Healthy Volunteers Get Two Doses in Trials

Acceptance by the U.S. Food and Drug Administration (FDA) as part of their Investigational New Drug (IND) program allowed Inovio to move forward with enrolling 40 healthy volunteers from Philadelphia’s Perelman School of Medicine at the University of Pennsylvania and the Center for Pharmaceutical Research in Kansas City, Missouri.13The first volunteers were injected with the experimental vaccine on April 5 and clinical trial participants each will be given two doses, four weeks apart.

The Phase 1 study is designed to evaluate immune system response and safety of Inovio’s DNA COVID-19 vaccine for use in humans. Preliminary data are expected by late summer and Inovio plans to immediately move on to Phase 2 studies to evaluate efficacy of the vaccine.

Inovio started working on its COVID-19 vaccine when the genetic sequence of the virus became available in early January 2020. The company has already produced thousands of doses of INO-4800, enough to supply both Phase 1 and Phase 2 studies. They plan to have one million doses of the vaccine available by the end of 2020, “for trials as well as emergency use, subject to regulatory guidance and funding.”14

In July 2019, Inovio announced positive results from a Phase 1 clinical trial testing of its experimental DNA vaccine for the Middle East Respiratory Syndrome (MERS),15a new coronavirus infection that emerged in 2012. MERS is associated with a high mortality rate of 12 to 86 percent.16

The DNA Vaccine Difference

According to the National Institute of Allergy and Infectious Diseases (NIAID),

“Traditional vaccines consist of entire pathogens that have been killed or weakened so that they cannot cause disease.” 17

Other vaccines developed in the late 20thcentury contain only microbe components, or antigens, that are thought to best stimulate an immune response and antibody production.

Licensed viral and bacterial vaccines that are in widespread use today are categorized as either killed inactivated, live attenuated, toxoid, or subunit vaccines.They contain antigens from lab altered viruses and bacteria, as well as adjuvants, such as aluminumor oil-in-water emulsion, to provoke stronger inflammatory responses for stimulating artificial immunity; preservatives, such as Thimerosal; stabilizers, such as MSGand gelatin; and residual substances from the manufacturing process, such as chemicals, antibiotics, human diploid cells, animal and insect cell proteins and other excipients.18

However, for the past several decades, scientists have been experimenting with creation of nucleic acid vaccineswhich, according to NIAID, “involves introducing genetic material encoding the antigen or antigensagainst which an immune response is sought. The body’s own cells then use this genetic material to produce the antigens.”19DNA vaccines like Inovio’s experimental COVID-19 vaccine (INO-4800) inject a small piece of circular DNA called a plasmid that carries genes encoding proteins from the pathogen (in this case, COVID-19) to provoke the cells into producing antibodies.

Writing in Biotech Primer, Emily Burke, PhD explained that, “the ‘visiting’ DNA prompts the host to produce the target viral protein and consequent immune response within their own cells, but without [causing] an infection. DNA vaccines try to stimulate the body’s cells to continue to reproduce the antigen. Burke commented on the difficulty of getting the body’s cells to accept injected DNA without further intervention and stated:20

“The key challenge for DNA/RNA vaccines is getting patients’ cells to accept the introduced genetic material. So far, the most effective technique seems to be electroporation–delivering short pulses of electrical current to the patient with the vaccine.The electricity creates temporary pores in a patient’s cell membranes, enabling the DNA/RNA to enter.”

DNA Vaccines: Gaps in Knowledge

DNA (and RNA) vaccines have been available and approved for veterinary medicine, but none have yet been approved for human use. Compared to traditional vaccines, nucleic acid (genetic) vaccines are less inexpensive and easier to manufacture because they consist only of DNA or RNA, which is taken up and translated into protein by host cells.21

The World Health Organization (WHO) acknowledges there are gaps in scientific knowledge about DNA vaccines and states:22

Many aspects of the immune response generated by DNA vaccines are not understood.However, this has not impeded significant progress towards the use of this type of vaccine in humans, and clinical trials have begun.

Some of the outstanding questions about DNA vaccine safety include:23

  • chronic inflammationbecause the vaccine continually stimulates the immune system to produce antibodies;
  • possible integration of plasmid DNA into the body’s host genome resulting in mutations;
  • problems with DNA replication;
  • triggering of autoimmune responses, and
  • activation of cancer-causing genes.

Inovio’s Electric Device Delivery System Drives DNA Into Body Cells

On Mar. 12, 2020 Inovio announced it had received a $5M grant from the Gates Foundation to accelerate the testing and scale up of CELLECTRA®3PSP proprietary hand held “smart device” running on batteries for the intradermal delivery of its DNA COVID-19 vaccine (INO-4800).The press release explained that electricity will be used to give people Inovio’s DNA vaccine in order to “open small pores in the cell reversibly to allow the plasmids to enter” so the “cell’s own machinery” can “generate coded antigens, which then stimulate an antibody response:”24

The next generation CELLECTRA 3PSP device is designed specifically for a COVID-19 type pandemic scenario. It is a small, portable, hand-held, user-friendly device that runs on readily available “AA” batteries… INOVIO’s DNA medicines deliver optimized plasmids directly into cells intramuscularly or intradermally using INOVIO’s proprietary hand-held smart device called CELLECTRA®.

CELLECTRA® uses a brief electrical pulse to open small pores in the cell reversibly to allow the plasmids to enter, overcoming a key limitation of other DNA and mRNA approaches. Once inside the cell, the plasmids are used by the cell’s own machinery to generate coded antigens, which then stimulate an immune response, thereby strengthening the body’s own natural defense mechanisms. Administration with the CELLECTRA device ensures that the DNA medicine is delivered directly into the body’s cells,where it can go to work immediately mounting an immune response.

The company added that, “INOVIO’s DNA medicines do not interfere with or change in any way an individual’s own DNA.”

Electroporation Not So Painless

Electroporation is defined as “a process of applying a high-voltage electrical pulse to a living cell, causing temporary permeability of the cell membrane, through which a foreign material such as DNA may pass.”25Over the past two centuries, electric fields have been used to kill microbes for food and water sterilization and, since the 1990s, biomedical researchers have investigated using reversible electroporation to temporarily destabilize cell membranes for the purpose of (1) fusing cells together through membrane destabilization (electrofusion); (2) introducing DNA material into cells through transient pores in the membrane (electrogenethearpy); and (3) delivering chemotherapeutic drugs directly into cells (electrochemotherapy). Irreversible electroporation uses a much higher electrical energy regime that induces cell death and is employed in certain types of therapies to treat cancer.2627

In 2013, researchers at Inovio and University of Pennsylvania division of Infectious Disease speculated about how electroporation and Inovio’s CELLECTRA® adaptive constant current device helps enhance vaccine DNA uptake by cells and generates a “more robust immune response:”28

Electroporation (EP) immune response enhancement may mechanistically be due to local inflammatory processes caused by the procedure itself.Electrical stimulation induces the secretion of inflammatory chemokines and cytokines and recruitment of monocytes, lymphocytes and antigen-presenting cells to the site of EP…As a result of these processes, both humoral and cell-mediated immunity is augmented compared with DNA injection alone, thus potentially enhancing vaccine efficacy.

The Inovio and University of Pennsylvania researchers noted that “A primary drawback of electroporation (EP) is pain and discomfort at the application sitecompared with convention injections.” In a small clinical trial, they evaluated the pain “tolerability” of the CELLECTRA® device by testing it on 10 healthy male adults given a sterile saline solution injection without any DNA, which was followed by application of electroporation using the Inovio device.

Nine out of ten subjects experienced mild to moderate injection site reactions of pain, tenderness, redness and swelling. There were also reaction reports of involuntary muscle contraction and mild to severe asymptomatic increases in CPK (creatine phosphokinase) levels in the blood of 6 participants.

According to Lab Tests Online, “creatine kinase (CK) is an enzymefound in the heart, brain, skeletal muscle, and other tissues. Increased amounts of CK are released into the blood when there is muscle damage.”29The researchers acknowledged that“The EP procedure has been shown to carry some potential of transient muscle damage in animal models, evident as increased numbers of fibers with central nucleoli and damaged myofibrillar bundles.”

At the end of the article, researchers discussed how EP could stimulate greater and longer lasting immune responses for experimental DNA vaccines being designed to prevent HIV and HPV. Although the 10 healthy male adults in the Inovio and University of Pennsylvania study did not get injected with DNA, the researchers explained that:30

EP must be applied immediately after DNA injection to exert its effect on gene expression…Inflammatory cell infiltration associated with the EP process may partially account for the increase in uptake. It is possible that antigen presentation is more efficient under stressful conditions in electrically stimulated cells and may create an adjuvant effect. Along these lines, EP has been shown to induce considerable lymphocytic infiltration, in addition to CPK elevationand skeletal muscle damage evident as lesions in mice.Because muscle tissue does not generally harbor many resident antigen-presenting cells, it is likely that recruitment to the injection site contributes to the efficacy of EP.


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2Carlson R. INO-4800 DNA Vaccine Description. Precision VaccinationsMar. 28, 2020.
3Inovio Pharmaceuticals, Inc. Inovio Initiates Phase 1 Clinical Trials of Its COVID-19 Vaccine and Plans First Dose Today. NasdaqApr. 6, 2020.
4FDA. Vaccine Product Approval Process. Jan. 30, 2018.
5College of Physicians of Philadelphia. Vaccine Development, Testing and Regulation. The History of VaccinesJan. 17, 2018.
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7Kelly E. The Race for a COVID-19 Vaccine. Science BusinessMar 23, 2020.
8U.S. Food and Drug Administration (FDA). Emergency Use Authorization (EUA). Feb. 7, 2020.
9Kilgore T. Inovio’s stock soars after receiving grant to develop coronoavirus vaccine. Market WatchJan. 24, 2020.
10Avril T. Inside a Philadelphia lab, scientists race to design a coronavirus vaccine. The Philadelphia InquirerFeb. 11, 2020.
11RTT News. Inovio, Bejing Advaccine to Advance Development of Vaccine Against Coronavirus. NasdaqJan. 30, 2020.
12Ology Bioservices and Inovio Pharmaceuticals, Inc. Ology Bioservices, Inovio Partner to Manufacture COVID-19 DNA Vaccine with $11.9 Million Department of Defense Grant.Press Release Mar. 24 2020.
13Etherington D. CDC. Vaccine Excipient Summary: Excipients Included in U.S. Vaccines, by Vaccine. February 2020.A Second Potential COVID-19 Vaccine, Backed By Bill And Melinda Gates, Is Entering Human Testing. Tech CrunchApr. 6, 2020.
14Dhaliwal S. NIAID. Vaccine Types. July 2019.Inovio Pharmaceuticals Begins Phase 1 Human Testing Of Its COVID-19 Vaccine.BenzingaApr. 7, 2020.
15Inovio Pharmaceuticals, Inc. Inovio’s Positive First-in-Humans MERS Vaccine Results Published in The Lancet Infectious Diseases. Press Release July 25, 2019.
16Dawson P, Malik MR et al. What Have We Learned about Middle East Respiratory Syndrome Coronavirus Emergence in Humans? A Systematic Literature Review. Vector Borne Zoonotic Dis2019; 19(3): 174-192.
17NIAID. Vaccine Types. July 2019.
18CDC. Vaccine Excipient Summary: Excipients Included in U.S. Vaccines, by Vaccine. February 2020.
19NIAID. Vaccine Types. July 2019.
20Burke E. DNA Vaccines Explained. Biotech Primer. March 31, 2020.
21DNA and RNA Vaccine Design.Creative BioLabs.
22World Health Organization (WHO). Biologicals: DNA Vaccines.
23Zhang A. DNA Vaccines: Scientific and Ethical Barriers to the Vaccines of the Future. Harvard College Global Health ReviewNov. 15, 2011.
24Inovio Pharmaceuticals, Inc. INOVIO Receives New $5 Million Grant to Accelerate Scale Up of Smart Delivery Device for Its COVID-19 Vaccine. Press Release Mar. 12, 2020.
25The Free Dictionary by Farlex. Definition of Electroporation.
26Rolong A, Davalos RV et al. History of Electroporation. In: Meijerink M., Scheffer H., Narayanan G. (eds) Irreversible Electroporation in Clinical Practice2018.
27Venbever R, Preat VV. In vivo efficacy and safety of skin electroporation. Adv Drug Deliv Rev.1999; 35(1): 77-78.
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29LabTests Online. Creatine Kinase (CK).Mar. 5, 2020.
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For more:

Various groups have uncovered that numerous COVID-19 vaccines have aborted fetal cell lines (PER C6 Ad5 technology) which not only has moral implications for many but safety concerns according to the FDA:

“Residual DNA in vaccines derived from tumorigenic cells, including those transformed by Ad5, can pose potential risks to the vaccine recipient in two respects: oncogenicity and infectivity. Each of these biological properties must be considered and evaluated for each cell substrate.” and http://Moderna mRNA-1273 Covid-19 Vaccine Uses Aborted Fetal Cells – Sanofi Pasteur’s Version Does Not

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