Looking at the DNA platform: An Alternative to mRNA-Delivered Technologies

DNA-encoded technologies are being used in the development of therapies and vaccines, and can be an alternative to the well-known mRNA platform. The mRNA platform was utilized for both the Pfizer-BioNTech and Moderna COVID-19 vaccines. The DNA and mRNA platforms have multiple differences. For example, in thinking about vaccines, DNA-enabled vaccines require an electrical impulse to push the genetic message into the cell, whereas RNA vaccines do not.

However, one commonality is that both DNA and RNA vaccines instruct cells in the body to produce a protein that induces an immune response.

David Weiner, PhD, The Wistar Institute executive vice president, director of the Vaccine & Immunotherapy Center, and W.W. Smith Charitable Trust Professor in Cancer Research, and his team have been working on DNA-encoded SARs-CoV-2 monoclonal antibodies, and earlier this year they were able to advance their research to a clinical trial.

The research included colleagues at The University of Pennsylvania, AstraZeneca, INOVIO Pharmaceuticals, and Indiana University. This summer they began their clinical trial using this novel COVID-19 antibody delivery approach. 

A Public-Private Partnership

An important component of any research is to have the financial backing to sustain what can be years of work in the quest to go from bench to bedside. COVID-19 research has been largely shaped by a combination of public-private partnerships to develop everything from vaccines to therapies for the virus.

These partnerships remind everyone that the federal government and private sector can work together to create significant accomplishments.

Wistar is a research organization that specializes in early-stage discovery science in the areas of cancer, immunology and infectious disease. They conducted their aforementioned work under a Defense Advanced Research Projects Agency (DARPA) and Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND) funded program.

“This development is the culmination of the many steps taken working together with our DARPA/JPEO leadership team and members of the consortium advancing this product at this important time. We look forward to seeing the initial outcome from this first-in-human clinical trial studying this novel concept,” Weiner said in a statement.

This team was awarded $37.6 million to fund the rapid pre-clinical development of DMAbs to prevent COVID-19. For the uninitiated, DMAbs use a person’s own cells as a factory for making the protective antibodies, simplifying the development and the production process for biologics—which could broaden the use of such novel medicines to the global community.

“In addition to assessing safety and tolerability, we will also look for important insights into biological expression and activity in our trial subjects and if these can be shown to impact viral infection,” Weiner stated of the trial.

Contagion spoke to Weiner about the differences in mRNA and DNA technologies, their work on DNA-encoded monoclonal antibodies, and some insights into the clinical trials.