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Since the advent of freezers, the life sciences sector has depended on them. This reliance stems from the necessity of storing and shipping numerous patient specimens, drug possibilities, and other biologics in efficient freezers or encased in dry ice to keep them stable.
The issue was starkly evident during the Covid-19 crisis when numerous shipments of vaccines had to be discarded because they had melted during transit. Currently, the stakes have escalated. Tailored medicine, ranging from CAR-T cell treatments to tumor DNA analysis that informs cancer therapies, relies on immaculate biological specimens. However, a single power failure, shipping holdup, or equipment malfunction can annihilate irreplaceable patient specimens, delaying treatment for weeks or stopping it completely. In remote regions and developing countries, the absence of dependable cold storage effectively bars entire communities from these life-saving innovations.
Cache DNA aims to liberate the field from freezers. At MIT, the company’s founders devised a novel method for preserving and storing DNA molecules at ambient temperatures. The company is now advancing biomolecule preservation technologies applicable in various health care scenarios, from routine blood analysis and cancer detection to rare disease investigations and pandemic readiness.
“We aspire to disrupt the existing paradigm,” states Cache DNA co-founder and former MIT postdoc James Banal. “For more than 50 years, biotech has relied on the cold chain. Why has this not evolved? Meanwhile, the expense of DNA sequencing has plummeted from $3 billion for the initial human genome to below $200 today. As DNA sequencing and synthesis become increasingly affordable and swift, storage and transport have emerged as the key obstacles. It’s akin to having a supercomputer that still depends on punch cards for data entry.”
As the company seeks to preserve biomolecules beyond DNA and scale its kit production, co-founders Banal and MIT Professor Mark Bathe believe their technology holds the promise to unlock new health revelations by making specimen storage accessible to scientists globally.
“Envision if every individual on Earth could contribute to a global biobank, not just those residing near costly freezer facilities,” Banal suggests. “That’s 8 billion biological narratives instead of just a select few. The remedies we are lacking might be concealed within the biomolecules of someone we have never been able to reach.”
From quantum computing to “Jurassic Park”
Banal emigrated from Australia to MIT to work as a postdoc under Bathe, a professor in MIT’s Department of Biological Engineering. Banal primarily operated within the MIT-Harvard Center for Excitonics, collaborating with researchers throughout MIT.
“I was involved in some quite unconventional projects, like DNA nanotechnology and its connection with quantum computing and artificial photosynthesis,” Banal reminisces.
Another project concentrated on utilizing DNA for data storage. While computers encode information as 0s and 1s, DNA can represent the same data using the nucleotides A, T, G, and C, allowing for exceptionally dense data storage: By one estimation, 1 gram of DNA can accommodate up to 215 petabytes of information.
After three years of effort, in 2021, Banal and Bathe established a system that stored DNA-based information in minuscule glass particles. They formed Cache DNA in the same year, securing the intellectual property by collaborating with MIT’s Technology Licensing Office while applying the technology for storing clinical nucleic acid samples as well as DNA-related data. Nonetheless, the technology was still too immature for most commercial applications at that time.
Professor of chemistry Jeremiah Johnson adopted a different strategy. His research demonstrated that certain plastics and rubbers could be rendered recyclable by incorporating cleavable molecular bonds. Johnson speculated that Cache DNA’s technology could be more rapid and reliable employing his amber-like polymers, similar to how researchers in the “Jurassic Park” film retrieved ancient dinosaur DNA from a tree’s fossilized amber resin.
“It originated basically as a playful conversation in the halls of Building 16,” Banal recalls. “He’d viewed my work, and I was acquainted with the advancements in his lab.”
Banal instantly recognized the potential. He was familiar with the challenges posed by the cold chain. For his MIT experiments, he stored specimens in large freezers maintained at -80 degrees Celsius. Sometimes, samples would go missing in the freezer or get buried under the inevitable ice buildup. Even when perfectly preserved, samples could deteriorate as they thawed.
As part of a partnership between Cache DNA and MIT, Banal, Johnson, and two researchers in Johnson’s lab developed a polymer that preserves DNA at room temperature. In homage to their inspiration, they showcased the approach by encoding DNA sequences with the “Jurassic Park” theme song.
The researchers’ polymers could envelop a material as a liquid and then transform into a solid, glass-like block when heated. To release the DNA, the researchers could incorporate a molecule named cysteamine and a specific detergent. The researchers demonstrated that the process could successfully store and access all 50,000 base pairs of a human genome without causing harm.
“Real amber is not particularly effective at preservation. It’s porous and allows moisture and air in,” Banal notes. “What we engineered is entirely different: a dense polymer network that forms an impermeable barrier around DNA. Imagine it like vacuum-sealing, but on a molecular scale. The polymer is so hydrophobic that water and enzymes that would typically destroy DNA simply cannot penetrate.”
As the research was progressing, Cache DNA discovered that sample storage represented a significant challenge for hospitals and research laboratories. In regions like Florida and Singapore, researchers reported that managing humidity’s impact on specimens was another ongoing challenge. Other scientists worldwide inquired whether the technology would assist them in collecting specimens beyond the laboratory.
“Hospitals conveyed that they were running out of space,” Banal states. “They had to discard samples, limit sample collection, and in extreme cases, resorted to decades-old storage technologies that result in degradation after a relatively short time. It became a guiding goal for us to address those challenges.”
A new tool for precision health
Last year, Cache DNA distributed over 100 of its initial alpha DNA preservation kits to researchers globally.
“We didn’t instruct researchers on what to use it for, and we were astonished by the various applications,” Banal remarks. “Some utilized it for collecting samples in the field where cold shipping was not an option. Others evaluated it for long-term archival storage. The applications varied, but the challenge was universal: They all required dependable storage without the limitations of refrigeration.”
Cache DNA has devised an entire array of preservation technologies that can be tailored for different storage situations. The company recently received a grant from the National Science Foundation to broaden its technology to preserve a wider range of biomolecules, including RNA and proteins, which could yield new health insights and understanding.
“This crucial innovation aids in removing the cold chain and has the capability to unlock millions of genetic samples globally for Cache DNA to facilitate personalized medicine,” Bathe asserts. “Eliminating the cold chain is half the equation. The other half is scaling from thousands to millions or even billions of nucleic acid samples. Combined, this could enable the equivalent of a ‘Google Books’ for nucleic acids stored at room temperature, whether for clinical samples in hospital settings and remote areas of the globe or alternatively to enable DNA data storage and retrieval on a large scale.”
“Freezers have dictated where research could be conducted,” Banal suggests. “Eliminate that limitation, and you begin to unveil possibilities: island nations investigating their unique genetics without samples perishing in transit; every rare disease patient globally contributing to research, not just those near significant hospitals; the 2 billion individuals lacking reliable electricity finally participating in global health studies. Room-temperature storage isn’t the complete solution, but every remedy commences with a sample that has endured the journey.”
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