The world is growing increasingly impatient with the pandemic, aching to fight it faster. A $37.6 million grant is powering a newly-formed consortium tasked with developing DNA-encoded antibodies, which can kill a COVID-19 infection faster than antibody treatments that don’t have the power of DNA. Adding even more speed to this strategy, the grant supports a two-year timeframe to reach Phase 2 clinical trials. “It’s incredibly fast,” says the Indiana University researcher tapped to play a role.
Assistant Professor of Molecular and Cellular Biochemistry Dr. Jesper Pallesen leads an IU lab with expertise in providing very detailed 3D structures of DNA-encoded antibodies and how they interact with SARS-CoV-2. The lab is part of the team formed by the $37 million grant from the Defense Advanced Research Projects Agency.
“Antibodies are the principle protein that your immune system produces in response to disease,” says Pallesen. “When there’s a pathogen in your body, eventually, your immune response will generate antibodies specific for that pathogen.”
The key word is “eventually.” The process is long for the immune system to recognize a foreign invader and build the antibodies to kill it. DNA is the difference-maker for developing a fast-acting treatment for patients fighting COVID-19; it puts the process in fast-forward.
All proteins—and in this case, antibodies—are encoded by DNA. Rather than waiting for the body to build the DNA that will power these COVID-19 fighting antibodies, Pallesen’s method provides the DNA.
“It takes a while for your immune system to arrive at a good recipe for good antibodies. We are speeding up the process for your body to produce really good antibodies by providing the recipe to do so, instead of asking your cells to find the recipe themselves,” says Pallesen. “Once we identify antibodies that are really good against a particular pathogen—SARS-CoV-2, for example—then we can produce DNA [in the lab] that specifically instructs a cell to create these antibodies that are already really good.”
Beyond speed, another major advantage of DNA-encoded antibodies is that the human body does most of the heavy lifting for “mass production.”
“Because [DNA-encoded antibodies] work instantly, you get what we call bioamplification. If we administer to a patient a little of the DNA that contains the recipe for an antibody, from each copy of DNA I administer, the patient’s body will produce lots and lots and lots of antibody copies,” says Pallesen. “That is very smart for manufacturing. We can get away with a given quantity of DNA we manufacture; we can treat many more patients than if we produce this at the protein level.”
Pallesen says, beyond the work that this grant is supporting, the DNA platform is also “incredibly important” to develop for vaccine purposes. Bioamplification is, again, a game-changer. DNA platforms could be used to encode a pathogenic protein, and when administered to a human being, it would elicit a greater vaccine response—and immediately, rather than weeks. Because the body is taking over the reproduction, DNA vaccines wouldn’t be at the mercy of manufacturing capacity, unlike today’s COVID-19 vaccines.
Perhaps even more important, says Pallesen, is that DNA vaccine platforms are very stable, even potentially at room temperature, which means “they’re easy to get to all corners of the world.” And in the U.S., cold chain storage complexities that are impacting the rollout of COVID-19 vaccines, for example, would be eliminated.
While the grant is supporting the war against COVID-19, Pallesen believes progress made with the coronavirus could inform broader efforts as well.
“I’m very excited to bring DNA-based platforms—for both therapeutics and vaccines—out of labs and clinical trials and to the bedside,” says Pallesen. “With this platform, we can service parts of the world that are currently not very easy to serve. Everyone deserves good treatment everywhere in the world, and this is a large step toward accomplishing that goal.”
Pallesen says DNA-based treatments—and on a broader scale, DNA vaccines—wouldn’t need to be kept cold because DNA is a very stable molecule.
Pallesen says the consortium, which includes AstraZeneca, the Wistar Institute, Inovio and the University of Pennsylvania, is well positioned to fast track its discoveries to the bedside.