Multiplexed in Vivo Disease Sensing with Nucleic Acid-Barcoded Reporters enabling CRISPR-Cas-based Detection

Aspects of the present disclosure relate to methods and compositions useful for in vivo and/or in vitro profiling of environmental triggers (e.g., enzyme activity, pH or temperature). In some embodiments, the disclosure provides methods of in vivo enzymatic processing of exogenous molecules followed by detection of modified nucleic acid barcodes as representative of the presence of active enzymes (e.g., proteases) associated with a disease, for example, cancer. In some embodiments, the disclosure provides compositions and methods for production of in vivo sensors comprising modified nucleic acid barcodes.