Synthetic serum markers enable noninvasive monitoring of gene expression in primate brains

Abstract

We demonstrate a noninvasive approach for measuring transgene expression in the brains of nonhuman primates using blood-based assays with engineered reporters termed released markers of activity (RMAs). RMAs cross the blood-brain barrier via reverse transcytosis, allowing detection of brain-derived markers in the bloodstream. Using this approach, we demonstrate repeated monitoring of multiple transgenes expressed in cortical and subcortical regions over several weeks. RMAs are sufficiently sensitive to detect circuit-specific, Cre-dependent adeno-associated viral (AAV) expression, and RMA signals are correlated with histological quantification of gene expression in neural tissue. Together, these findings establish the RMA platform as a cost-efficient and repeatable tool for neuroscience studies in nonhuman primates, enabling sensitive and multiplexed measurement of brain gene expression with a simple blood test.