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.