New erasable serum markers reveal fast, subtle changes in brain gene activity

Monitoring gene activity in the brain just got a major upgrade. Rice University bioengineers have developed a novel serum marker system that can be erased in the bloodstream, enabling researchers to capture subtle changes in brain activity that previously went unnoticed.

Tracking how genes switch on and off in the brain is crucial for understanding neurological disorders, but traditional tools are often invasive or fail to detect small changes over time. One promising alternative involves engineered serum markers—small proteins produced by targeted brain cells that travel into the bloodstream, where they can be measured with a simple blood test.

These molecules, known as released markers of activity (RMAs), are highly sensitive but persist in the blood for hours, which can mask short-term fluctuations. Rice researchers have now engineered an erasable version of RMAs that can be selectively cut apart by an enzyme inside the bloodstream, effectively resetting the signal and allowing for a fresh reading.

Jerzy Szablowski, assistant professor of bioengineering at Rice and a corresponding author on the study, said, The key advance here is a new way of thinking about serum markers ⎯ that we can modify them inside the bloodstream when we need to. This broad concept has many potential applications, ranging from extending the marker s half-life to improve detectability, or erasing them to remove the background signal and improve temporal resolution.

Signal reset, subtle changes In animal tests, a single injection of the cleaving enzyme removed roughly 90% of the RMAs background signal within 30 minutes. This reset revealed gene-expression changes that had previously been undetectable. Researchers also demonstrated that the process could be repeated to measure how quickly the markers returned, providing a dynamic picture of gene activity over time.

Shirin Nouraein, a graduate student at Rice and first author on the study, explained, Using this enzyme, we separated the domain that provides signal from the domain that makes it last a long time in blood, making the background signal decay within minutes. We found a significant elevation in signal changes when we used these markers to track the dynamics of gene expression in the brain. Beyond neurology, erasable serum markers could transform diagnostics across medicine. The ability to edit marker behavior in the body opens opportunities for detecting tumors or lung diseases with minimally invasive urine or blood tests.

Brain research, broader impact The project reflects Rice s strategic focus on brain research and aligns with the mission of the Rice Brain Institute, recently launched to accelerate technologies for understanding and treating neurological disorders. The research was supported by the National Institutes of Health and the National Science Foundation. Currently, markers are usually extracted from the body and interpreted as-is, which limits their usefulness, Szablowski noted. This new method gives us a way to actively manage the signal and improve temporal resolution.

By creating serum markers that can be erased and renewed inside the bloodstream, Rice researchers are setting the stage for a future where clinicians could monitor brain activity and treatment responses with unprecedented precision, all through simple, minimally invasive testing. The full study is published in Proceedings of the National Academy of Sciences.