PHILADELPHIA -- (September 12, 2019) -- The Wistar Institute has received a grant of approximately $4.6 million from the National Institutes of Health in support of innovative research to tackle antibiotic resistance.
Antimicrobial resistance (AMR) represents an expanding global public health concern. While antibiotic-resistant organisms are appearing at an alarming rate, there has been a 30-year hiatus in the development of novel classes of antibiotics for combatting these infections. Multidrug-resistant Pseudomonas aeruginosa is one of the top microorganisms on the list of priority AMR pathogens compiled by the World Health Organization.
A Wistar team led by David B. Weiner, Ph.D., executive vice president, director of the Vaccine & Immunotherapy Center, and the W.W. Smith Charitable Trust Professor in Cancer Research at Wistar, is advancing a novel, nontraditional approach to combat multidrug-resistant P. aeruginosa, based on a synthetic DNA technology called DNA-encoded monoclonal antibodies (DMAbs). In a recent study, Weiner and colleagues developed a targeted DMAb approach for AMR and demonstrated that these DMAbs can effectively control multidrug-resistant P. aeruginosa infection in mice.
This grant will now allow for extension of these studies by providing the researchers with $4,624,553 over four years to further implement the DMAb strategy and move it forward toward clinical development.
The Weiner lab developed DMAb technology by designing genetic sequences directly encoding monoclonal antibodies into an optimized DNA platform. These gene sequences are administered in vivo to be expressed locally at the site of injection. The recipient receives a gene-encoded blueprint instructing their cells to produce the encoded monoclonal antibody specifically targeting the bacteria. DMAbs can be developed simply and quickly and are produced directly in the patient, dramatically lowering production timeline and costs associated with manufacturing of conventional antibodies; furthermore, DMAbs do not require expensive cold chain storage and are suitable for delivery in combinations.
"Engineered synthetic DMAbs represent a transformative approach to the production of biomolecules directly in the patient," said Weiner. "We are honored to receive this funding and feel it is an important recognition of the promise of DMAbs for the growing threat of antibiotic resistance. This support will move us closer to creating an out-of-the-box tool to fight antibiotic-resistant infections that threaten the lives of thousands every year just in the U.S."
Co-investigators on the grant are assistant professor Farokh Dotiwala, M.B.B.S., Ph.D., associate professor Daniel Kulp, Ph.D., and research assistant professor Ami Patel, Ph.D., of Wistar's Vaccine & Immunotherapy Center. Inovio Pharmaceuticals is a collaborator on the grant.
The multidisciplinary team will work collaboratively to enhance the existing P. aeruginosa DMAb platform and develop more potent options with improved antigen binding and receptor engagement. They will be further tested in preclinical models to support translation of this DMAb approach and ultimately move it forward to human studies.
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.