In a groundbreaking leap for neuroscience and gene therapy, Rice University bioengineer Jerzy Szablowski and his colleagues have unveiled a transformative method for noninvasively monitoring gene expression in living primate brains. Their findings, recently published in the prestigious journal Neuron, showcase a novel technology based on synthetic protein reporters known as released markers of activity (RMAs). These engineered proteins, designed to surmount the formidable blood-brain barrier and remain detectable in peripheral blood samples, open an unprecedented window into the dynamic molecular activity of the brain without requiring invasive procedures.
Traditionally, studying gene expression within the brain has posed enormous challenges due to the organ’s complexity and the protective nature of the blood-brain barrier, which shields neural tissue from most circulating molecules. Existing imaging and biopsy techniques provide only limited snapshots, often invasive and unable to track gene activity longitudinally in the same individual. This revolutionary RMA platform addresses these constraints by encoding synthetic proteins capable of crossing from the brain into the bloodstream. The presence and concentration of these markers in blood serum directly reflect underlying gene expression patterns within specific brain regions, enabling continuous and minimally intrusive monitoring.
The research team validated this technology in nonhuman primates, notably rhesus macaques, marking a critical advance beyond previous experiments conducted in rodent models. This cross-species translational success was achieved by precisely adapting protein domains responsible for blood-brain barrier transit from mouse to primate versions, thereby facilitating the reporters’ functional deployment in higher mammals. Consequently, this platform promises to bridge the translational gap between small animal neuroscience and human clinical applications—a notorious bottleneck in neurogenetics and therapeutic development.
What makes the RMA approach particularly powerful is its sensitivity and multiplexing potential. Unlike conventional imaging modalities that detect broad anatomical changes or metabolic shifts, RMAs can sensitively track activity in clusters as small as tens to hundreds of neurons, with molecular specificity to particular gene targets. Furthermore, the technology is configurable to incorporate an array of synthetic serum markers in parallel, enabling simultaneous multiplexed profiles of gene expression from different brain regions or cell types. Advanced biochemical techniques like mass spectrometry or single-molecule protein sequencing can decode these complex serum signatures, providing a high-dimensional molecular fingerprint of brain function.
This capability is expected to revolutionize several domains of neuroscience research and clinical monitoring. Longitudinal tracking of gene expression dynamics through simple blood draws will allow investigators to capture the temporal progression of neurological diseases, brain plasticity, or cognitive adaptation. This is especially critical in disorders where pathology evolves gradually over months or years, such as addiction, Huntington’s disease, and other neurodegenerative conditions. By “watching the movie instead of taking a snapshot,” the scientific community gains an opportunity to unravel causal molecular pathways and intervene at stages previously invisible to researchers.
The inception of the RMA platform was inspired by earlier challenges with antibody-based therapies failing to persist within the brain due to rapid translocation into the bloodstream. Szablowski’s ingenious solution was to isolate and repurpose the protein domains intrinsic to antibodies that mediate their transport across the blood-brain barrier. By fusing these domains with customizable reporter proteins, they engineered molecules capable of being expressed in neurons, secreted into the extracellular space, and eventually routed to the blood in a sustainable and quantifiable manner.
Collaborative efforts with Vincent Costa’s lab at Emory University were instrumental in validating the RMA technology in primates and demonstrating its practical advantages over traditional imaging approaches. Costa emphasizes that this platform drastically reduces the resource burdens and technical barriers typical of longitudinal primate neuroscience research. Such efficiency gains accelerate the generation of critical translational insights and promise to hasten the pathway toward human applications of gene monitoring technologies.
Financial support from the David and Lucile Packard Foundation and the National Institutes of Health was central to this multidisciplinary accomplishment, reflecting the broader community’s recognition of the urgent need for innovative tools in brain research. The combined expertise of molecular biology, bioengineering, psychiatry, and behavioral sciences integrated to push this frontier, illustrating how open scientific exchange can propel breakthroughs in brain health.
Looking ahead, the implications of the RMA platform extend far beyond experimental neuroscience. Envisioning clinical contexts, the capacity to obtain detailed, longitudinal gene expression profiles through routine blood tests might transform diagnostics, prognostics, and personalized treatment strategies for a vast array of brain disorders. This modality could enable dynamic monitoring of therapeutic responses in real time, refining the efficacy and safety of gene therapies, pharmacological interventions, and behavioral treatments.
As the scientific community continues to explore and optimize synthetic serum markers, the versatility and specificity of the platform are likely to grow. Custom-designed RMAs targeting genes relevant to synaptic function, neuroinflammation, or neurodegeneration can unlock mechanistic insights previously inaccessible. Moreover, integration with emerging protein sequencing technologies will yield unprecedented resolution and throughput, empowering a new era of precision neurobiology driven by molecular biomarkers harvested noninvasively from accessible biofluids.
In summary, the development of synthetic serum markers for noninvasive gene expression monitoring represents a watershed moment in neuroscience. By enabling the direct translation of molecular brain activity into peripheral blood signals, Szablowski, Costa, and their teams have furnished researchers and clinicians with a potent toolset to track neuronal dynamics over time with sensitive spatial and genetic specificity—an innovation poised to reshape brain science and medicine in the coming decades.
Subject of Research: Animals
Article Title: Synthetic Serum Markers Enable Noninvasive Monitoring of Gene Expression in Primate Brains
News Publication Date: 27-Feb-2026
Web References:
References:
- Lee, S., Romac, M., Watanabe, S., Chernov, M., Li, H., Raisley, E., Rothenhoefer, K., Dahlquist, Z., Szablowski, J., & Costa, V. (2026). Synthetic Serum Markers Enable Noninvasive Monitoring of Gene Expression in Primate Brains. Neuron. https://doi.org/10.1016/j.neuron.2026.01.003
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Keywords
Brain, Blood, Blood brain barrier, Amygdala, Striatum, Luciferases, Transgenes, Primates, Gene therapy, Gene expression
