Differentiating Between DNA and mRNA Platforms

The Wistar Institute in Philadelphia, Pa, is involved in cancer, immunology and infectious disease research, and vaccine development. The research center advances basic research, translating fundamental discoveries into future therapies to benefit global health and training the next generation of scientific leaders.

Ami Patel, PhD, assistant professor, Vaccine & Immunotherapy Center, Wistar Institute, leads a laboratory team at the center. A major area of study with her team has been around employing non-viral DNA vectors for vaccine and antibody delivery. Patel’s most recent studies include DNA vaccine development against Ebola virus, Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and multiple studies in the rapidly advancing field of DNA-encoded monoclonal antibodies (DMAbs).

Of course, everyone is familiar with the mRNA platform from the pandemic and the subsequent COVID-19 vaccines. However, not much is known to the public about how DNA vaccines and monoclonal antibodies work.

“DNA itself is a very inherently stable molecule. It has a very large coding capacity, and so that allows us to put very large synthetic genes inside DNA,” Patel said. “mRNA is really kind of an in-between step between DNA and protein synthesis. And when you have an mRNA platform, you get very rapid protein production. It's kind of an in-between way to kick start that process. And so, it's very rapid; it's a very burst of expression. But then it's finished with synthetic DNA. It mostly takes place in the nucleus, and you get multiple copies of mRNA coming off of that DNA molecule. And so, you can have a longer period of expression, and a longer period of protein expression afterwards, following translation. This allows us to encode genes in a different way and to get different types of immune responses, for example, or different types of protein production than you would get from a short burst from an mRNA platform.”

One of the interesting differences in DNA and mRNA is that the former is temperature stable, and it allows it to be used internationally more easily. “Being temperature stable, it helps enable some of these properties for delivery to resource limited settings, such as low and middle income countries, because it doesn't necessarily have to have the cold chain that's attached to it like mRNA,” she said.

Patel spoke at last week’s World AMR Congress, and her presentation, “Tackling Pandemic Pathogens: Gene-Encoded Antibodies as Pre-Exposure Prophylaxis,” discussed some of her work around the DNA platform.

Whereas, vaccines have been a long established modality to prevent diseases and viruses; monoclonal antibodies (DMAbs) are a newer area of study with the hope of bringing immunization of diseases. One example Patel points out is the monoclonal antibody, nirsevimab-alip (Beyfortus), to prevent RSV in the infant population. It was FDA approved last year. In fact, it is the first-ever prophylactic product indicated for the prevention of RSV lower respiratory tract disease (LRTD) in newborns and infants born during or entering their first RSV season, and for children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season. Patel says the approval of this immunization has really opened the door to this line of research.

Although monoclonal antibodies might be a newer area of interest, it is not one that will likely reduce vaccines' roles in reducing illness. Patel sees vaccines and monoclonal antibodies as complementary, and not competing, prophylactic modalities.

“I like to think of vaccines as a way to induce active immunity. So basically you're delivering this protein or this coding sequence, and your body's developing its own immune response to it and its own antibodies and own T cells in an active form. So it's really requiring active engagement of your body," Patel said. "Something like DNA encoded antibodies, you're delivering the antibody already in almost a passive form, so your body doesn't have to develop its own immune response. It now has that end product antibody already, and so you can think of them working hand in hand together.”

She mentions there are some groups that do not respond well to vaccines and monoclonal antibodies are a way of delivering that type of passive immunity and a way to supplement their immune responses.