The U.S. Defense Advanced Research Projects Agency (DARPA) has awarded $12.2 million toward research into developing DNA-based monoclonal antibodies (mAbs) for three areas of infectious disease.
Researchers from the Perelman School of Medicine at the University of Pennsylvania; Inovio Pharmaceuticals; and MedImmune, the global biologics research and development arm of AstraZeneca will develop and assess the DNA mAbs in influenza virus, Pseudomonas aeruginosa, and Staphylococcus aureus.
MedImmune developed the first mAb approved by the FDA for the prevention of an infectious disease, while Inovio pioneered the development of optimized DNA-based vaccines and immunotherapies using electroporation. The project proposes an entirely new technology, initially developed at UPenn in the lab of David Weiner, Ph.D., professor of pathology and laboratory medicine, to develop a platform designed to rapidly protect people against emerging infections through synthetic antibodies produced by the patients themselves.
The UPenn-developed technology has been licensed by Inovio, which disclosed the DARPA grant today.
While mAbs have been developed for a variety of diseases, they remain expensive and time consuming to produce and study: They typically requiring costly large-scale laboratory development and production because they are manufactured outside the body, require frequent repeat administrations, and have limited duration of effectiveness.
The partnership reasons that these limitations can be overcome by DNA-based mAbs due to their simplified design, product stability, manufacturing, dosing frequency, and cost effectiveness.
DNA for a mAb is encoded in a DNA plasmid containing optimized DNA sequences encoded to generate disease-specific mAbs. The plasmids are produced using cost-effective and highly-scalable fermentation techniques, and delivered directly into cells of the body using electroporation, with the encoded mAbs then produced by these cells.
Using synthetic DNA plasmids delivered using electroporation, the team will construct and evaluate multiple DNA mAbs. The collaboration aims to show that the DNA plasmids can activate sufficient quantities of specific antibodies in the body to be protective against a pathogen challenge—thus providing potential new avenues for treatment of disease.
Previously published studies show that a single administration of a highly optimized DNA-based mAb targeting HIV virus in mice generated antibody molecules in the bloodstream, according to Inovio.
“Our DNA-based mAbs demonstrated robust virus neutralization and protected treated animals challenged with a lethal virus,” J. Joseph Kim, Ph.D., Inovio's president and CEO, said in a statement. “Monoclonal antibody technology has already achieved multiple market-proven product successes, and we believe DNA-based mAb technology could significantly extend the medical benefits and efficiency of this concept.”
A successful completion of the initial preclinical activities covered by the DARPA grant is intended to lead to clinical studies on selected product candidates, which the partners expect the agency would fund through a future increment to the grant award.
DARPA is an agency of the U.S. Department of Defense that creates and supports new technologies deemed to have importance for national security. DARPA was established in 1958 “to prevent strategic surprise from negatively impacting U.S. national security and create strategic surprise for U.S. adversaries by maintaining the technological superiority of the U.S. military,” according to its website.