Monitoring in vivo transcription with synthetic serum markers

ABSTRACT Understanding transcription profiles of living tissues is critical for biology and medicine. However, measurement of the transcript levels is typically done in homogenized tissues post-mortem. Here, we present a new platform that enables non-invasive monitoring of specific mRNA levels in vivo , without tissue destruction. We achieved this by combining two cutting-edge tools - synthetic serum markers, called Released Markers of Activity ( RMAs ), and RNA-based sensors of transcription. We call this platform IN-vivo Tracking of ACtive Transcription, or INTACT . In INTACT, when the target mRNA is expressed, the RNA sensor detects it and triggers the production and release of RMA reporters into the blood. Once in blood, the RMAs can be easily measured through a simple blood draw. Our data shows that INTACT can measure transcription of transgenes, as well as endogenous transcripts, such as c-Fos or Arc , both in vivo in the brain and in tissue culture. INTACT enables simple measurement of transcript level histories in genetically-targetable cell populations of living animals.