Summary: A new noninvasive method now makes it possible to monitor gene expression and cellular activity in the living brain through a simple blood test. Researchers have translated a blood-to-brain reporting platform—released markers of activity (RMAs)—from mice into rhesus macaques, demonstrating a viable path toward human application and enabling much finer, longitudinal insight into brain health than current imaging techniques allow.
Released markers of activity (RMAs) are engineered protein reporters that cross the blood-brain barrier and enter the bloodstream, carrying information about which genes are active in specific neurons. Unlike MRI, PET or tissue biopsy, this blood-based approach lets scientists repeatedly sample the same individual over time to construct continuous timelines of molecular and cellular changes in the brain. That capability is especially valuable for studying progressive neurological conditions such as addiction, Huntington’s disease and other disorders where gene expression dynamics drive disease stages.
Key Facts
- Blood-brain reporting: RMAs are synthetic proteins designed to exit the brain into the blood, providing a readout of transgene and endogenous gene expression from targeted neurons.
- Primate translation: The platform, previously validated in mice, functions effectively in rhesus macaques—an essential translational milestone before testing in humans.
- High sensitivity: RMAs can detect activity from very small neuronal populations, on the order of tens to hundreds of cells, a precision level beyond current noninvasive imaging.
- Longitudinal sampling: Because measurements are taken from blood, researchers can perform repeated sampling to observe how gene expression evolves over days, weeks or months.
- Multiplexed measurement: Different RMAs can be designed to report on multiple genes and brain regions simultaneously and detected in a single blood sample with techniques such as mass spectrometry or single-molecule protein sequencing.
Source: Rice University
Gene therapies have already shown benefit for several disorders, including immune deficiencies, inherited blindness, hemophilia and newly reported work in Huntington’s disease. The recent study published in Neuron extends that progress by presenting a noninvasive monitoring tool that could accelerate development of personalized neurotherapies. Rice University bioengineer Jerzy Szablowski and collaborators in Vincent Costa’s lab at Emory University demonstrate that RMAs—engineered to cross the blood-brain barrier and persist in circulation for hours—provide reliable blood-borne signals of brain gene expression in nonhuman primates, matching performance seen in mice.
Large animal studies are a crucial step toward clinical translation, and many laboratory innovations never reach this stage. The success in rhesus macaques therefore represents a meaningful advance. According to Szablowski, modifying a short protein domain that controls exit from the brain was sufficient to adapt the reporter between species. This observation underscores how a relatively small molecular change—replacing the mouse version of the domain with the rhesus version—restored reporter function in the primate brain.
Beyond sensitivity, RMAs are flexible: investigators can design multiple serum markers to monitor distinct genes or circuits simultaneously. Szablowski notes that protein detection is naturally multiplexable, so a single blood draw could yield large-scale, region- and gene-specific datasets using mature biochemical tools.
Longitudinal monitoring of gene expression in the living brain can reveal when and where disease-driving molecular events begin and how they unfold. Szablowski uses addiction as an example: rather than a single terminal or biopsy snapshot, repeated RMA sampling produces a “movie” of molecular changes that shows which genes are driving progression and when therapeutic interventions would be most effective.
Emory collaborator Vincent Costa adds that eliminating the need for complex, repeated brain imaging dramatically improves feasibility for primate neuroscience studies. By reducing the time, cost and logistical bottlenecks of conventional imaging, the RMA platform enables long-term, detailed experiments needed to bridge results from animal models to human treatments.
Funding: The research received support from the David and Lucile Packard Foundation (2021-73005) and the National Institutes of Health (R01MH125824, P51OD011132, P51OD011092).
Key Questions Answered
A: No. The technology reports molecular and cellular states—specifically which genes are being turned on or off in particular neurons—not thoughts or subjective mental content. It reveals how the brain is changing biologically in response to disease, drugs or other interventions, which is critical for developing targeted therapies.
A: Moving from rodents to primates is one of the largest translational hurdles in neuroscience. Demonstrating that the RMA platform functions in rhesus macaques indicates the approach is robust across species and supports further evaluation for human clinical trials.
A: Current tools often provide only late-stage or low-resolution views of disease. RMAs enable detection of the precise moment and location where disease-related gene expression begins to change, opening a window for earlier intervention to prevent irreversible damage.
Editorial Notes
- This article was edited by a Neuroscience News editor.
- The journal paper was reviewed in full by the editorial team.
- Additional context was added by staff to clarify translational implications.
About this neurotech research news
Author: Silvia Cernea Clark
Source: Rice University
Contact: Silvia Cernea Clark, Rice University
Image: Image credited to Neuroscience News
Original Research: Open access. “Synthetic Serum Markers Enable Noninvasive Monitoring of Gene Expression in Primate Brains” by Sangsin Lee, McKenna Romac, Sho Watanabe, Mykyta Chernov, Honghao Li, Emma Raisley, Kathryn Rothenhoefer, Zachary Dahlquist, Jerzy Szablowski and Vincent Costa. Neuron. DOI: 10.1016/j.neuron.2026.01.003
Abstract
Synthetic Serum Markers Enable Noninvasive Monitoring of Gene Expression in Primate Brains
This work demonstrates a noninvasive method for measuring transgene expression in nonhuman primate brains using blood-based assays and engineered reporters called released markers of activity (RMAs). RMAs traverse the blood-brain barrier through reverse transcytosis, enabling detection of brain-derived markers in circulation. The approach supports repeated monitoring of multiple transgenes expressed in cortical and subcortical regions over several weeks. RMAs show sensitivity sufficient to detect circuit-specific, Cre-dependent AAV expression, and circulating RMA signals correlate with histological measures of gene expression in neural tissue. Collectively, these results establish RMAs as an affordable, repeatable tool for sensitive and multiplexed measurement of brain gene expression via a simple blood test in nonhuman primates.