In a groundbreaking development, scientists have pioneered a new technique for preserving biological materials like RNA and proteins in a solid-state, akin to a pill or tablet. This innovation dissolves in water for immediate use, offering a solution to the current challenges in storing and handling products derived from living cells, which are often used in health care and scientific research.
Biological materials, including mRNA, enzymes, and antibodies, are crucial in the creation of new medicines and diagnostic tools. However, they are highly sensitive to changes in environmental conditions during storage, transportation, and handling. If not stored and handled correctly, these materials can degrade or become inactive, limiting their accessibility, particularly in resource-limited and underserved communities.
The Pfizer COVID vaccine rollout, for instance, was hampered by the need for deep freezers for storage and transport. Even when refrigeration infrastructure is available, failures occur in over 10% of cases, leading to over $35 billion in losses annually, according to the IQVIA Institute for Human Data Science.
Now, a team of researchers at California Polytechnic State University (Cal Poly) in San Luis Obispo, CA, has developed this novel method for storing biological materials, which holds immense potential for the scientific and medical communities. Findings from the recent work were published in ACS Synthetic Biology.
The majority of pharmaceutical drugs are stored in various forms, such as liquids, powders packaged in capsules, pills, and tablets. Each form plays a crucial role in how the medication is stored and used. However, apart from a few exceptions, biological materials are currently limited to being stored as frozen or refrigerated liquids and freeze-dried powders. This lack of a tablet-like form has hindered the field, often making it difficult to reach the locations and users where they are needed.
Dr. Javin Oza, associate professor in chemistry and biochemistry, who led the research on the new storage platform, said, “Just as tablets have changed the way we take medications, the solid-state storage platform opens new possibilities for how we handle and use biological materials, unlocking the potential for existing therapies and emerging biotechnologies.”
Most biological materials require storage as liquids, which are frozen in deep freezers for the duration of their shelf life. This is achieved through a complex and integrated system of refrigerators and freezers known as the cold chain. In recent years, many research teams, including the group at Cal Poly, have made progress in freeze-drying biological materials, which has improved the way they are stored and handled, but the use of freeze-drying remains limited.
The solid-state storage of biologics represents a significant advancement, as tablets provide unique advantages to better preserve the material they encapsulate. For instance, the innovation allows researchers to package biological materials into tablets that can be stored on a shelf at room temperature and added to water to be dissolved for on-demand use. In addition to ensuring the stability and activity of the biological materials, solid-state storage has been developed to ensure that tablets quickly disintegrate and dissolve into water.
“Our innovation makes storing and using biologics as easy as an Alka-Seltzer tablet, just drop it into water, mix, and it’s ready to go,” Oza added.
The team demonstrated the solid-state storage platform’s ability to support a complex mixture of biologics by showing that the cell’s machinery, capable of decoding genetic information into making RNA and proteins, can be stored in a solid state. When added to water, the machinery reactivates to decode genetic information as if it were still within the cell. The team also demonstrated that emerging biotechnology tools such as CRISPR can be activated after storage in a solid state.
In order to unlock the broad applications of existing and emerging biological technologies, we report the development of a novel solid-state storage platform for complex biologics. The resulting solid-state biologics (SSB) platform meets four key requirements: facile rehydration of solid materials, activation of biochemical activity, ability to support complex downstream applications and functionalities, and compatibility for deployment in a variety of reaction formats and environments,” the authors wrote. “As a model system of biochemical complexity, we utilized crude Escherichia coli cell extracts that retain active cellular metabolism and support robust levels of in vitro transcription and translation. We demonstrate broad versatility and utility of SSB through proof-of-concepts for on-demand in vitro biomanufacturing of proteins at a milliliter scale, the activation of downstream CRISPR activity, as well as deployment on paper-based devices.”
The team’s results show potential for a wide range of applications. The ability to store biologics at room temperature and activate them on demand could be useful for delivering therapeutics to remote locations where the cold chain is unavailable. For instance, one could envision portable, on-demand production of vaccines in remote locations. The platform could also be used for diagnostic testing of anything from COVID-19 screening to testing wastewater contaminants simply by changing the composition of the tablets. For utilization in the field, solid-state storage has the added benefit of being simple to use, reducing the need for specialty training of technicians, and further improving access at the point of need.
Further improvements to the platform will be needed to suit specific use cases. The researchers anticipate that additional modifications such as coatings could help the solid-state storage be more suitable for withstanding extreme environments such as heat, humidity, and chemicals. Additionally, continued improvements in treatments and coatings to the solid-state biologics could lead to biological medication tablets that can be taken orally rather than through injections. If successful, medications such as insulin and Humira (immunosuppressive treatment for arthritis) could someday be taken orally rather than through injections, improving the quality of life for millions of people.
As the field of biotechnology is growing rapidly, the potential impacts extend beyond healthcare and into biomanufacturing, education, and research. The innovation is also likely to impact the way biologics are transported around the globe and into space for the on-demand production of life-saving therapies.