Synthetic Serum Markers Enable Noninvasive Monitoring of Gene Expression in Primate Brains

We demonstrate a noninvasive approach to measure transgene expression in the brain of nonhuman primates using blood tests with engineered reporters called Released Markers of Activity ( RMAs ). RMAs can exit the brain and enter the bloodstream via reverse-transcytosis across the blood-brain barrier. We demonstrate that these reporters can be used to repeatedly monitor expression of multiple transgenes in cortical and subcortical brain regions simultaneously over a period of two months. RMAs are also sensitive enough to detect circuit-specific Cre-dependent AAV expression. Through this study, the RMA platform provides a cost-efficient, noninvasive tool for neuroscience study of large animals, enabling sensitive, multiplexed, and repeatable measurements of gene expression in the brain with a blood test.