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This MIT spinout is taking biomolecule storage out of the freezer
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.”
New RNA tool to advance cancer and infectious disease research and treatment
Researchers at the Antimicrobial Resistance (AMR) interdisciplinary research group of the Singapore-MIT Alliance for Research and Technology (SMART), MIT’s research enterprise in Singapore, have developed a powerful tool capable of scanning thousands of biological samples to detect transfer ribonucleic acid (tRNA) modifications — tiny chemical changes to RNA molecules that help control how cells grow, adapt to stress, and respond to diseases such as cancer and antibiotic‑resistant infections. This tool opens up new possibilities for science, health care, and industry — from accelerating disease research and enabling more precise diagnostics to guiding the development of more effective medical treatments for diseases such as cancer and antibiotic-resistant infections.
For this study, the SMART AMR team worked in collaboration with researchers at MIT, Nanyang Technological University in Singapore, the University of Florida, the University at Albany in New York, and Lodz University of Technology in Poland.
Addressing current limitations in RNA modification profiling
Cancer and infectious diseases are complicated health conditions in which cells are forced to function abnormally by mutations in their genetic material or by instructions from an invading microorganism. The SMART-led research team is among the world’s leaders in understanding how the epitranscriptome — the over 170 different chemical modifications of all forms of RNA — controls growth of normal cells and how cells respond to stressful changes in the environment, such as loss of nutrients or exposure to toxic chemicals. The researchers are also studying how this system is corrupted in cancer or exploited by viruses, bacteria, and parasites in infectious diseases.
Current molecular methods used to study the expansive epitranscriptome and all of the thousands of different types of modified RNA are often slow, labor-intensive, costly, and involve hazardous chemicals, which limits research capacity and speed.
To solve this problem, the SMART team developed a new tool that enables fast, automated profiling of tRNA modifications — molecular changes that regulate how cells survive, adapt to stress, and respond to disease. This capability allows scientists to map cell regulatory networks, discover novel enzymes, and link molecular patterns to disease mechanisms, paving the way for better drug discovery and development, and more accurate disease diagnostics.
Unlocking the complexity of RNA modifications
SMART’s open-access research, recently published in Nucleic Acids Research and titled “tRNA modification profiling reveals epitranscriptome regulatory networks in Pseudomonas aeruginosa,” shows that the tool has already enabled the discovery of previously unknown RNA-modifying enzymes and the mapping of complex gene regulatory networks. These networks are crucial for cellular adaptation to stress and disease, providing important insights into how RNA modifications control bacterial survival mechanisms.
Using robotic liquid handlers, researchers extracted tRNA from more than 5,700 genetically modified strains of Pseudomonas aeruginosa, a bacterium that causes infections such as pneumonia, urinary tract infections, bloodstream infections, and wound infections. Samples were enzymatically digested and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), a technique that separates molecules based on their physical properties and identifies them with high precision and sensitivity.
As part of the study, the process generated over 200,000 data points in a high-resolution approach that revealed new tRNA-modifying enzymes and simplified gene networks controlling how cells respond and adapt to stress. For example, the data revealed that the methylthiotransferase MiaB, one of the enzymes responsible for tRNA modification ms2i6A, was found to be sensitive to the availability of iron and sulfur and to metabolic changes when oxygen is low. Discoveries like this highlight how cells respond to environmental stresses, and could lead to future development of therapies or diagnostics.
SMART’s automated system was specially designed to profile tRNA modifications across thousands of samples rapidly and safely. Unlike traditional methods, this tool integrates robotics to automate sample preparation and analysis, eliminating the need for hazardous chemical handling and reducing costs. This advancement increases safety, throughput, and affordability, enabling routine large-scale use in research and clinical labs.
A faster and automated way to study RNA
As the first system capable of quantitative, system‑wide profiling of tRNA modifications at this scale, the tool provides a unique and comprehensive view of the epitranscriptome — the complete set of RNA chemical modifications within cells. This capability allows researchers to validate hypotheses about RNA modifications, uncover novel biology, and identify promising molecular targets for developing new therapies.
“This pioneering tool marks a transformative advance in decoding the complex language of RNA modifications that regulate cellular responses,” says Professor Peter Dedon, co-lead principal investigator at SMART AMR, professor of biological engineering at MIT, and corresponding author of the paper. “Leveraging AMR’s expertise in mass spectrometry and RNA epitranscriptomics, our research uncovers new methods to detect complex gene networks critical for understanding and treating cancer, as well as antibiotic-resistant infections. By enabling rapid, large-scale analysis, the tool accelerates both fundamental scientific discovery and the development of targeted diagnostics and therapies that will address urgent global health challenges.”
Accelerating research, industry, and health-care applications
This versatile tool has broad applications across scientific research, industry, and health care. It enables large-scale studies of gene regulation, RNA biology, and cellular responses to environmental and therapeutic challenges. The pharmaceutical and biotech industry can harness it for drug discovery and biomarker screening, efficiently evaluating how potential drugs affect RNA modifications and cellular behavior. This aids the development of targeted therapies and personalized medical treatments.
“This is the first tool that can rapidly and quantitatively profile RNA modifications across thousands of samples,” says Jingjing Sun, research scientist at SMART AMR and first author of the paper. “It has not only allowed us to discover new RNA-modifying enzymes and gene networks, but also opens the door to identifying biomarkers and therapeutic targets for diseases such as cancer and antibiotic-resistant infections. For the first time, large-scale epitranscriptomic analysis is practical and accessible.”
Looking ahead: advancing clinical and pharmaceutical applications
Moving forward, SMART AMR plans to expand the tool’s capabilities to analyze RNA modifications in human cells and tissues, moving beyond microbial models to deepen understanding of disease mechanisms in humans. Future efforts will focus on integrating the platform into clinical research to accelerate the discovery of biomarkers and therapeutic targets. The translation of the technology into an epitranscriptome-wide analysis tool that can be used in pharmaceutical and health-care settings will drive the development of more effective and personalized treatments.
The research conducted at SMART is supported by the National Research Foundation Singapore under its Campus for Research Excellence and Technological Enterprise program.