Funding for DNA Vaccines to Fight Infectious Disease
News Oct 22, 2014
The Defense Advanced Research Projects Agency (DARPA) has awarded $12.2 million for a collaborative study by scientists from the Perelman School of Medicine at the University of Pennsylvania; Inovio Biosciences, Inc; and MedImmune Inc., the global biologics research and development arm of AstraZeneca, Inc. The group will develop DNA-based monoclonal antibodies (mAbs) for infectious disease treatment. DARPA is an agency of the US Department of Defense that creates and supports novel technologies important for national security.
Together, the three organizations will develop and assess the DNA mAbs in preclinical studies using technology developed by Penn and licensed by Inovio. The collaboration will focus on three disease areas – influenza-causing microbes, Pseudomonas aeruginosa and Staphylococcus aureus.
MedImmune developed the first mAb approved by the U.S. Food & Drug Administration for the prevention of an infectious disease, and Inovio pioneered the development of optimized DNA-based vaccines and immunotherapies using an efficient delivery mechanism called electroporation. The project proposes an entirely new technology, initially developed at Penn in the lab of David Weiner, PhD, professor of Pathology and Laboratory Medicine, to provide a platform to rapidly protect people against emerging infections through the development of novel synthetic antibodies produced by the patients themselves.
“We are excited about this important collaboration focused on investigating the potential utility of synthetic DNA-based monoclonal antibodies to develop new ways to control difficult-to-treat infectious diseases,” says Weiner. “We have assembled a team with complementary capabilities in research, biologics, and delivery technology to work toward this common goal.”
A Different Type of Vaccine
Over the last few decades, monoclonal antibodies (mAbs) have become one of the most important approaches to treat a variety of diseases, however they remain expensive and time consuming to produce and study. They are manufactured outside the body, typically requiring costly large-scale laboratory development and production, and also require frequent repeat administrations and have a limited duration of potency in the body.
DNA-based mAbs have the potential to overcome these limitations by virtue of their simplified design, product stability, manufacturing, dosing frequency, and cost effectiveness, thereby providing potential new avenues for treatment of disease.
The shift seen in new mAb technologies is that the DNA for a monoclonal antibody is encoded in a DNA plasmid, which is produced using very cost effective and highly scalable fermentation techniques. These plasmids are delivered directly into cells of the body using electroporation and the encoded mAbs are then produced by these cells. Using this approach, previously published studies show that a single administration of a highly optimized DNA-based monoclonal antibody targeting HIV virus in mice generated antibody molecules in the bloodstream.
This collaboration aims to demonstrate that the DNA plasmids containing optimized DNA sequences encoded to generate disease-specific mAbs can activate sufficient quantities of specific antibodies in the body to be protective against a pathogen challenge. Using the capabilities and advantages of synthetic DNA plasmids delivered using electroporation, the team will construct and evaluate multiple DNA mAbs.
Successful completion of the initial preclinical activities under the DARPA grant aims to lead to clinical studies on selected product candidates to be funded under a future increment to the award.
Inside cells, where DNA is packed tightly in the nucleus and rigid proteins keep intricate transport systems on track, some molecules can simply self-organize, find one another in crowded spaces, and quickly coalesce into droplets. Now, new research shows how proteins that organize into liquid droplets inside cells make certain biological functions possible.