Discovering Biomarkers with RNA-Based Technology: A Breakthrough in Medical Diagnostics
Biomarkers are valuable indicators of health conditions, from chronic inflammatory diseases like arthritis and heart disease to acute cases like bacterial and viral infections. However, conventional tests for detecting and measuring biomarkers are often expensive, ranging from $100 to over $1,000 per test. This can restrict their accessibility and usefulness in medical diagnostics. However, researchers at Penn State have developed a low-cost RNA-based technology that can detect and measure biomarkers efficiently and affordably. This technology uses riboswitches, sensor molecules that can bind to specific biomarkers and activate or deactivate an observable signal.
The Advantages of RNA-Based Technology for Biomarker Detection
The researchers combined a cell-free expression system with engineered riboswitch sensors to create a cost-effective solution for biomarker detection. Unlike conventional detection methods, cell-free expression systems are not restricted by cell walls or membranes, allowing bulky proteins to enter them and be measured. Riboswitches can be engineered to detect any biomarker of interest, from proteins to nucleic acids. Besides, riboswitch sensors can be synthesized from DNA instructions using a cell-free expression system, a low-cost and efficient process.
The researchers tested riboswitch sensors with three proteins to demonstrate their efficacy: MS2, a small protein found on a bacterial phage, and the medically relevant biomarkers human monomeric C-reactive protein and human interleukin-32 gamma. Out of the 32 riboswitches designed to detect these proteins, most successfully detected their target proteins. The researchers also used computational optimization and thermodynamic modeling to design riboswitch sensors more efficiently. Their design algorithm, called the Riboswitch Calculator, can generate DNA instructions for more sensitive and reliable riboswitch sensors.
The Potential of RNA-Based Technology for Medical Diagnostics
The development of RNA-based technology could revolutionize medical diagnostics. These sensors could help doctors diagnose patients promptly and efficiently. Patients would no longer have to endure several expensive tests, and doctors would get more comprehensive and accurate information about their patients’ health. RNA-based technology could also facilitate the development of new medical devices for diagnosing a range of diseases.
Furthermore, RNA-based sensors have several advantages over conventional detection methods:
They are low-cost and efficient, requiring only DNA instructions and a cell-free expression system to synthesize them.
They are highly specific and sensitive, able to detect and measure biomarkers accurately and reliably.
They are versatile and can be engineered to detect any biomarker of interest.
They can be freeze-dried and rehydrated, making them easy to store and transport without requiring cold chain storage and distribution of samples.
They have potential applications in fields outside medicine, such as environmental monitoring, agriculture, and biotechnology.
Conclusion
The development of RNA-based technology for detecting biomarkers is a breakthrough in medical diagnostics. The low cost, high sensitivity, specificity, and versatility of RNA-based sensors make them ideal for diagnosing a range of health conditions, from chronic inflammatory diseases to acute infections. The Riboswitch Calculator developed by Penn State researchers is a new tool for designing and optimizing riboswitch sensors with high sensitivity and reliability. RNA-based sensors have potential applications outside medicine and could revolutionize fields like environmental monitoring and agriculture. The cost-effective and scalable nature of RNA-based technology makes it accessible to a wide range of healthcare providers and patients, indicating a bright future for the field of medical diagnostics.
Summary
Penn State researchers have developed RNA-based technology that can detect and measure biomarkers cost-effectively. Their technology combines a riboswitch sensor that can bind to specific biomarkers with a cell-free expression system that reads DNA and synthesizes riboswitch sensors. Using computational optimization and thermodynamic modeling, the researchers have designed a riboswitch calculator tool that can generate DNA instructions for creating more sensitive and reliable riboswitch sensors. Their technology can detect important human disease biomarkers like C-reactive protein or interleukin-32 gamma, which indicate chronic or acute conditions like arthritis and bacterial infections. The researchers anticipate that diagnostic devices for healthcare providers could emerge as a result of this technology, benefiting patients and healthcare professionals alike. RNA-based technology also has potential applications outside of medicine, including environmental monitoring, agriculture, and biotechnology.
Additional Perspective
The potential benefits of RNA-based technology transcend medical diagnostics. The low cost and versatility of these sensors mean they have a range of applications in the field of biotechnology. For example, RNA-based sensors could facilitate the detection of environmental toxins and pollutants. The specificity and reliability of these sensors make them ideal for monitoring water quality, air pollution, and soil contamination, providing valuable data for environmental authorities. Besides, RNA-based sensors could help detect genetic mutations or changes in gene expression associated with certain diseases or conditions. In agriculture, RNA-based sensors could identify pathogens that cause crop diseases, improving crop yields and reducing crop losses.
Overall, RNA-based technology represents a significant leap forward in biomarker detection, offering patients, healthcare providers, and industries accurate, efficient, and affordable diagnostic tools. Future research in optimizing these sensors will multiply the value of these cutting-edge tools, helping society address environmental challenges and contributing to better public health outcomes.
References:
1. Penn State News. (2021, August 23). Penn State researchers develop low-cost, RNA-based technology to detect biomarkers. https://news.psu.edu/story/671604/2021/08/23/research/penn-state-researchers-develop-low-cost-rna-based-technology
2. Salis, H., Vezeau, G., & Gadila, L. (2021). Sensing protein biomarkers with riboswitches: from rational design to functional characterization. Nature Communications, 12(1), 1-14. doi: 10.1038/s41467-021-24903-1
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Penn State researchers have developed a low-cost RNA-based technology to detect and measure biomarkers, which can help decode the body’s physiology. The presence of protein biomarkers can indicate chronic or acute conditions, from arthritis to cancer and bacterial infections, for which conventional tests can cost anywhere from $100 to more than $1,000. New technology can perform the same measurement for about a dollar.
The team published their results in nature communications, combining the efforts of Howard Salis, associate professor of biological engineering, chemical engineering, and biomedical engineering; Grace Vezeau, who earned a Ph.D. in biological engineering from Penn State in 2021; and Lipika Gadila, who earned a Bachelor of Science in chemical engineering from Penn State in 2018.
The results demonstrate that RNA-based sensors can be designed to detect human biomarker proteins, including monomeric C-reactive protein, which is involved in chronic inflammatory conditions such as heart disease and arthritis, and interleukin-32 gamma, a signaling protein. for acute infections. such as viruses or bacterial infections. According to Salis, such sensors could be used to develop devices for diagnostic testing.
“These tests can help a doctor diagnose a patient, but it is more informative to measure multiple biomarkers periodically over several weeks,” Salis said. “Right now, a test can be expensive, and it adds up. With our new RNA-based technology, it’s now possible to do the same measurements for much less.”
The technology is a combination of a cell-free expression system and engineered RNA-based sensors called riboswitches. Cell-free expression systems contain cellular machinery to read DNA and make proteins, but are not restricted by cell membranes and allow bulky proteins to enter freely. Riboswitches are designed to bind to a biomarker protein and regulate the activation or repression of an observable signal. The riboswitch itself is produced within the cell-free expression system from the instructions of the DNA. In total, the cost of these materials is about a dollar per reaction.
According to Salis, this is the first time that researchers have designed a riboswitch sensor to detect biomarker proteins. The challenge, she said, is to discover the best DNA instructions to generate the most sensitive protein sensors.
“Previous efforts to design such riboswitch sensors have largely relied on trial-and-error experimentation, for example, building and characterizing large random libraries to identify riboswitch variants, the genetic blueprints and aptamers, that perform best,” Salis said. “Using a combination of thermodynamic modeling and computational optimization, we rationally designed new riboswitches that are predicted to be excellent protein sensors, and then tested them. Our design algorithm is called the Riboswitch Calculator.”
Salis and the researchers tested their new technology to detect three proteins: MS2, a small protein found on a bacterial phage, as proof of principle; and the medically relevant biomarkers human monomeric C-reactive protein and human interleukin-32 gamma. The researchers designed 32 riboswitches, most of which successfully detected their target proteins.
“Today’s assays require expensive detection reagents, expensive and bulky instruments, cold chain storage and distribution of samples, and trained personnel,” Salis said. “By applying computational modeling and design, we designed low-cost protein sensors that can be freeze-dried and rehydrated. The next step is to develop an easy-to-use device that allows researchers and clinicians to use this new technology.”
Salis is also affiliated with the Penn State Institutes of Energy and Environment.
The Defense Advanced Research Projects Agency and the Air Force Office of Scientific Research supported this research.
https://www.sciencedaily.com/releases/2023/06/230601155931.htm
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