Synthetic DNA-encoded monoclonal antibodies make the recipient’s body the production plant
Credit: The Wistar Institute
PHILADELPHIA — (Dec. 15, 2020) — A team of scientists from The Wistar Institute, INOVIO, AstraZeneca, the Perelman School of Medicine at the University of Pennsylvania, and Indiana University has received a $37.6 million award over two years from the Defense Advanced Research Projects Agency (DARPA) and the Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND) for rapid preclinical development and translational studies of DNA-encoded monoclonal antibodies (DMAbs) as countermeasures for COVID-19.
DMAbs, unlike conventional therapeutic antibodies, are administered as genetic blueprints that instruct the patient’s body to build its own highly specific antibodies against pathogens, such as bacteria and viruses, and as immunotherapeutics for cancer. Conceptually DMAbs have advantages over traditional monoclonal antibodies in scale-up and delivery, which would rapidly benefit large populations.
Worldwide, more than 72 million people are infected with SARS-CoV-2 and more than 1.6 million have died. The U.S. outbreak alone has resulted in the hospitalization of over 110,000 people. Sixteen million Americans have been infected, and more than 300,000 have died of COVID-19 since the outbreak began.*
Wistar scientists and their collaborators pioneered the development of DMAb technology as a unique asset to combat the COVID-19 pandemic. In addition to their high specificity for the target, DMAbs have important advantages of rapid manufacturing, low cost of production, and temperature-stable storage and distribution.
The concept of synthetic DMAb technology was originated in the laboratory of David B. Weiner, Ph.D., Wistar executive vice president, director of the Vaccine & Immunotherapy Center, and the W.W. Smith Charitable Trust Professor in Cancer Research. The technology involves the design and delivery of genetic sequences that encode monoclonal antibodies into an optimized DNA platform. This genetic blueprint is then administered to a person so that their own body becomes the production site of highly specific antibodies which, in the case of SARS-CoV-2, target essential parts of the virus. In animal studies, DMAbs have been applied to prevent infection as well as to treat infection.
“We are thrilled that DARPA and JPEO-CBRND have chosen Wistar to assemble this exceptional team to focus on advancing potential DMAb countermeasures for the SARS-CoV-2 crisis,” said Weiner. “Our team combines many different strengths to advance this approach from the bench to the bedside at lightening speed. We have a strong track record of working together to advance DNA-based solutions into the clinic and look forward to advancing these first-in-human studies as a possible risk mitigation approach for COVID-19.”
This paradigm-shifting award supports a unique public-private collaboration, which includes world-class capabilities in synthetic DNA therapeutics and monoclonal antibody technology. Together, with the support of exceptional clinical and translational teams and a global pharmaceutical company, this multidisciplinary approach is uniquely suited to address the unprecedented global health crisis brought about by COVID-19.
The program goal will be to rapidly design, enhance and scale SARS-CoV-2-specific DMAbs, and move them into laboratory and animal model studies. If successful, this will provide the foundation for rigorous, first-in-human clinical trials.
“This partnership broadens the scope and application of our DNA medicines platform across the spectrum of needed COVID-19 treatment modalities and opens the door for faster, more cost effective, and scalable production of monoclonal antibody products for other infectious diseases, cancers and other unmet medical needs,” said J. Joseph Kim, Ph.D., president and CEO of INOVIO. “Working with our partners, we are excited about the potential this offers both for situations requiring immediate clinical response and benefit.”
Mark Esser, VP and Head of Microbial Sciences, AstraZeneca, said, “We are excited to combine capabilities with Wistar and this world-class team to evaluate the potential of these DNA-delivered antibodies to impact the way we can respond to prevent and treat infection.”
“This COVID-19 pandemic presents a unique and immediate challenge to the world, one in which DNA treatments have the potential to move us to a future where COVID-19 is much more manageable,” said Pablo Tebas, M.D., a professor of Infectious Diseases at the Perelman School of Medicine at the University of Pennsylvania. “We are eager to build upon previous DMAb research and put it to the test against COVID-19.”
“We are very excited and honored to be part of this extraordinary team,” said Jesper Pallesen, Ph.D., assistant professor of molecular and cellular biochemistry at Indiana University. “The promise of DMAb technology is huge, and its implementation into our global anti-COVID-19 efforts will leave a resonating and lasting footprint. We are delighted to bring structural biology expertise to the team and to provide atomic-detail evaluation of DMAb technology efficacy mechanisms.”
Wistar, INOVIO, and the University of Pennsylvania with the Department of Defense and the Coalition for Epidemic Preparedness Innovations (CEPI) are in late-stage studies of a synthetic DNA vaccine for COVID-19. Through the collaboration with JPEO-CBRND, this work is supported by the Office of the Assistant Secretary of Defense for Health Affairs with funding from the Defense Health Agency.
Grant information: Synthetic DNA-encoded monoclonal antibodies (DMAbs) targeting COVID-19, 2020-2022.
*Data from the Johns Hopkins Coronavirus Research Center and The COVID Tracking Project at The Atlantic.
The Wistar Institute is an international leader in biomedical research with special cancer, immunology, infectious disease research, and vaccine development. Founded in 1892 as the first independent nonprofit biomedical research institute in the United States, Wistar has held the prestigious Cancer Center designation from the National Cancer Institute since 1972. The Institute works actively to ensure that research advances move from the laboratory to the clinic as quickly as possible. wistar.org.
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