Rice University researchers have developed a groundbreaking method to enhance the sensitivity of serum markers, enabling clearer brain activity signals. These markers, known as released markers of activity (RMAs), are small proteins produced by targeted brain cells and can be measured through a simple blood test. However, their long half-life can interfere with the detection of subtle changes in biological signals.
To address this challenge, the team designed an erasable marker that can be cleaved by an enzyme inside the bloodstream, effectively resetting the signal and allowing for new readings. This innovative approach, published in the Proceedings of the National Academy of Sciences, has the potential to revolutionize diagnostic capabilities.
Jerzy Szablowski, assistant professor of bioengineering at Rice University, explains, "We've introduced a novel concept for serum markers, allowing us to modify them within the bloodstream when needed. This approach offers flexibility in extending the marker's half-life for improved detectability or erasing them to enhance temporal resolution. Current practices often involve extracting markers from the body and interpreting them as-is, limiting their effectiveness."
In animal models, a single injection of the cleaving enzyme effectively removed approximately 90% of the RMAs' background signal within half an hour. This reset capability enabled the observation of subtle gene expression changes that were previously undetectable. The researchers also demonstrated the ability to repeat this process and measure the marker's reappearance, providing valuable insights into gene activity over time.
This method has the potential to transform clinical practice by enabling precise detection of issues or changes in patient responses to treatment through simple, minimally invasive testing. Shirin Nouraein, a graduate student involved in the study, highlights the significance of this development: "We've made the RMAs sensitive to a targeted protease, an enzyme that can cleave them. By separating the signal-providing domain from the long-lasting domain, we've achieved rapid background signal decay within minutes. This approach significantly enhances signal changes when tracking gene expression dynamics in the brain."
The implications of this research extend beyond neurology. The ability to edit markers inside the body allows for customization of their behavior for various diagnostic purposes. For instance, RMAs could be utilized for tumor or lung disease detection through urine tests.
This project exemplifies Rice University's dedication to brain research and aligns with the university's commitment to leading health innovations. It also aligns with the mission of the Rice Brain Institute, which aims to accelerate technologies for understanding and treating brain disorders.
The research was supported by the National Institutes of Health (DP2EB035905) and the National Science Foundation (1842494). The authors emphasize that the content in this press release solely represents their views and does not necessarily reflect the official positions of funding organizations and institutions.
