MIT Spinout Revolutionizes Biomolecule Storage

Massachusetts Institute of Technology

Ever since freezers were invented, the life sciences industry has been reliant on them. That's because many patient samples, drug candidates, and other biologics must be stored and transported in powerful freezers or surrounded by dry ice to remain stable.

The problem was on full display during the Covid-19 pandemic, when truckloads of vaccines had to be discarded because they had thawed during transport. Today, the stakes are even higher. Precision medicine, from CAR-T cell therapies to tumor DNA sequencing that guides cancer treatment, depends on pristine biological samples. Yet a single power outage, shipping delay, or equipment failure can destroy irreplaceable patient samples, setting back treatment by weeks or halting it entirely. In remote areas and developing nations, the lack of reliable cold storage effectively locks out entire populations from these life-saving advances.

Cache DNA wants to set the industry free from freezers. At MIT, the company's founders created a new way to store and preserve DNA molecules at room temperature. Now the company is building biomolecule preservation technologies that can be used in applications across health care, from routine blood tests and cancer screening to rare disease research and pandemic preparedness.

"We want to challenge the paradigm," says Cache DNA co-founder and former MIT postdoc James Banal. "Biotech has been reliant on the cold chain for more than 50 years. Why hasn't that changed? Meanwhile, the cost of DNA sequencing has plummeted from $3 billion for the first human genome to under $200 today. With DNA sequencing and synthesis becoming so cheap and fast, storage and transport have emerged as the critical bottlenecks. It's like having a supercomputer that still requires punch cards for data input."

As the company works to preserve biomolecules beyond DNA and scale the production of its kits, co-founders Banal and MIT Professor Mark Bathe believe their technology has the potential to unlock new health insights by making sample storage accessible to scientists around the world.

"Imagine if every human on Earth could contribute to a global biobank, not just those living near million-dollar freezer facilities," Banal says. "That's 8 billion biological stories instead of just a privileged few. The cures we're missing might be hiding in the biomolecules of someone we've never been able to reach."

From quantum computing to "Jurassic Park"

Banal came to MIT from Australia to work as a postdoc under Bathe, a professor in MIT's Department of Biological Engineering. Banal primarily studied in the MIT-Harvard Center for Excitonics, through which he collaborated with researchers from across MIT.

"I worked on some really wacky stuff, like DNA nanotechnology and its intersection with quantum computing and artificial photosynthesis," Banal recalls.

Another project focused on using DNA to store data. While computers store data as 0s and 1s, DNA can store the same information using the nucleotides A, T, G, and C, allowing for extremely dense storage of data: By one estimate, 1 gram of DNA can hold up to 215 petabytes of data.

After three years of work, in 2021, Banal and Bathe created a system that stored DNA-based data in tiny glass particles. They founded Cache DNA the same year, securing the intellectual property by working with MIT's Technology Licensing Office, applying the technology to storing clinical nucleic acid samples as well as DNA data. Still, the technology was too nascent to be used for most commercial applications at the time.

Professor of chemistry Jeremiah Johnson had a different approach. His research had shown that certain plastics and rubbers could be made recyclable by adding cleavable molecular bonds. Johnson thought Cache DNA's technology could be faster and more reliable using his amber-like polymers, similar to how researchers in the "Jurassic Park" movie recover ancient dinosaur DNA from a tree's fossilized amber resin.

"It started basically as a fun conversation along the halls of Building 16," Banal recalls. "He'd seen my work, and I was aware of the innovations in his lab."

Banal immediately saw the potential. He was familiar with the burden of the cold chain. For his MIT experiments, he'd store samples in big freezers kept at -80 degrees Celsius. Samples would sometimes get lost in the freezer or be buried in the inevitable ice build-up. Even when they were perfectly preserved, samples could degrade as they thawed.

As part of a collaboration between Cache DNA and MIT, Banal, Johnson, and two researchers in Johnson's lab developed a polymer that stores DNA at room temperature. In a nod to their inspiration, they demonstrated the approach by encoding DNA sequences with the "Jurassic Park" theme song.

The researchers' polymers could encompass a material as a liquid and then form a solid, glass-like block when heated. To release the DNA, the researchers could add a molecule called cysteamine and a special detergent. The researchers showed the process could work to store and access all 50,000 base pairs of a human genome without causing damage.

"Real amber is not great at preservation. It's porous and lets in moisture and air," Banal says. "What we built is completely different: a dense polymer network that forms an impenetrable barrier around DNA. Think of it like vacuum-sealing, but at the molecular level. The polymer is so hydrophobic that water and enzymes that would normally destroy DNA simply can't get through."

As that research was taking shape, Cache DNA was learning that sample storage was a huge problem from hospitals and research labs. In places like Florida and Singapore, researchers said contending with the effects of humidity on samples was another constant headache. Other researchers across the globe wanted to know if the technology would help them collect samples outside of the lab.

"Hospitals told us they were running out of space," Banal says. "They had to throw samples out, limit sample collection, and as a last-case scenario, they would use a decades-old storage technology that leads to degradation after a short period of time. It became a north star for us to solve those problems."

A new tool for precision health

Last year, Cache DNA sent out more than 100 of its first alpha DNA preservation kits to researchers around the world.

"We didn't tell researchers what to use it for, and our minds were blown by the use cases," Banal says. "Some used it for collecting samples in the field where cold shipping wasn't feasible. Others evaluated for long term archival storage. The applications were different, but the problem was universal: They all needed reliable storage without the constraint of refrigeration."

Cache DNA has developed an entire suite of preservation technologies that can be optimized for different storage scenarios. The company also recently received a grant from the National Science Foundation to expand its technology to preserve a broader swath of biomolecules, including RNA and proteins, which could yield new insights into health and disease.

"This important innovation helps eliminate the cold chain and has the potential to unlock millions of genetic samples globally for Cache DNA to empower personalized medicine," Bathe says. "Eliminating the cold chain is half the equation. The other half is scaling from thousands to millions or even billions of nucleic acid samples. Together, this could enable the equivalent of a 'Google Books' for nucleic acids stored at room temperature, either for clinical samples in hospital settings and remote regions of the world, or alternatively to facilitate DNA data storage and retrieval at scale."

"Freezers have dictated where science could happen," Banal says. "Remove that constraint, and you start to crack open possibilities: island nations studying their unique genetics without samples dying in transit; every rare disease patient worldwide contributing to research, not just those near major hospitals; the 2 billion people without reliable electricity finally joining global health studies. Room-temperature storage isn't the whole answer, but every cure starts with a sample that survived the journey."

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