At Rice University in Houston, bioengineers have cracked a problem that neuroscientists have long grappled with: how to peek inside a living brain and watch genes turn on and off, without cutting tissue or destroying the organism. The breakthrough, called INTACT (In-vivo Tracking of Active Transcription), works through something elegantly simple—a blood test.
Understanding which genes are active in the brain at any moment is transformative for medicine. It would let doctors track how the brain responds to medication, how an illness progresses, or even catch signs of neurological disease before symptoms appear. Until now, researchers could only analyze gene activity by destroying tissue samples—a method that tells you what genes were doing at one frozen moment in time, not how they dance and shift in a living organism over weeks or months.
Jerzy Szablowski, an assistant professor of bioengineering at Rice, and his team developed INTACT by combining two cutting-edge technologies. The first is an engineered molecular messenger called a Released Marker of Activity (RMA), which Szablowski's lab originally created. The second is a sensor that detects when a target gene becomes active, then triggers the production and release of these RMAs into the bloodstream. Once in the blood, the markers can be detected with a simple test—no biopsy required.
"This is the first demonstration of measuring transcription for targeted genes nondestructively in living tissue," Szablowski said. The elegance of the approach lies in its programmability. Rather than creating a custom reagent for each gene researchers want to study, the targeting is simply programmed into the genetic construct. "In theory," Szablowski explained, "should allow monitoring any gene by simply including its sequence in a genetic construct." This matters because it means INTACT could eventually track genes associated with Parkinson's, Alzheimer's, or any specific neural circuit—and new targets could be added without redesigning the entire system.
Sho Watanabe, a postdoctoral researcher and first author on the study published in Nature Communications, described the innovation as bringing together two recent technologies "to establish a new in vivo interface—monitoring of transcription in living tissues." The researchers demonstrated the platform in an animal model, proving it could simultaneously track gene expression across three different brain regions at once.
The implications ripple outward. Existing methods like next-generation sequencing and quantitative polymerase chain reaction have revolutionized molecular research by allowing scientists to track many genes collectively rather than one at a time. But both require destroying the sample—they work only on excised tissue or cells in a dish. INTACT changes the game by tracking living tissue over time, opening a window onto how the brain actually functions in a living organism.
Szablowski's vision reaches beyond neuroscience. "In the future, we want to make this omics revolution possible in living tissue," he said. Watanabe added that INTACT could eventually be applied not just to the brain but to monitoring gene expression in any tissue. His next project will draw on his earlier work in muscle biology and extracellular vesicles—the molecules cells use to communicate—to explore how synthetic mechanisms might enable dialogue between different organs and regions of the body.
The work, published in Nature Communications in 2026, represents a foundational step toward a future where doctors might routinely track gene activity through a simple blood draw, watching disease unfold in real time and adjusting treatment accordingly.