taRNAdigrada
Engineering the future of mRNA vaccines.
Stabilizing the fickle mRNA biomolecule is how medicine will advance. And that starts here.
The Challenge
The Covid-19 pandemic saw the world’s first-ever mass rollout of mRNA vaccines, critical to stopping the virus in its tracks. But mRNA vaccines — as with all RNA molecules — are notoriously difficult to transport and store. They often require ultra-cold storage and cold-chain supply lines that run up expenses, pollute the environment, and prevent rural or impoverished communities from accessing the potentially life-saving shots.
Urban areas like our hometown of Richardson, Texas aren’t free from risk, either, especially as natural disasters become more common worldwide due to climate change. In 2021, a major snowstorm knocked out power in our city, and our university health clinic alone lost over $20,000 of vaccines because of cold storage failures. The total damages and delays caused by these vaccines’ loss number in thousands of patients and tens of thousands of dollars.
Our Solution
In the aftermath of that loss, our goal was to engineer mRNA vaccines with improved stability, capable of surviving long-term in refrigerated or room-temperature environments. To do this, we turned to tardigrades — extremophile microorganisms famous for their ability to survive freeze-drying, desiccation and irradiation that would kill nearly any other organism — and the intrinsically-disordered proteins that grant them this stress tolerance.
We selected 10 stress-protective tardigrade proteins, cloned their genes into plasmids, expressed them in mammalian cells, and purified them. Next, we generated fluoroprotein mRNA through in vitro transcription to act as a proxy for vaccine mRNA. We combined this mRNA with each of the 10 proteins and subjected each mixture to a wide range of temperatures. This included common storage conditions (-80°C, -20°C, and 4°C) as well as ambient and high-heat stress conditions (room temperature and 50°C). We then measured the mRNA's relative degradation in vitro to assess stability in each condition.
The Impact
Preserving mRNA functionality against threats like radiation and high temperatures will open a whole new world in vaccine design, allowing the development of products that can be stored and transported to where they’re needed most. By helping mRNA reconstitute itself and continue functioning after dehydration or freeze-drying, long-term and low-cost storage will become tomorrow’s new normal instead of a far-off possibility. And these protein protectants could even be explored for stabilizing traditional vaccines made from antigens or dead pathogens.
mRNA wasn’t just a pandemic-era one-off — it is the future of vaccine design and countless other medical, biotechnological and research applications.