* ABSTRACT:

Microbes living and interacting with host cells in the human gut are essential to human health. Changes in the composition of this gut microbiome cause disease-associated symptoms, which motivates the engineering of microbes to diagnose, treat, memorize, or prevent disease. Microbes reprogrammed using advanced DNA-based recording systems are envisaged as emerging living diagnostics and therapeutics for a wide range of diseases and play key roles in regulating gut microbiota to treat disease in a non-invasive manner. Here, we present a CRISPR-aided genetic switch that uses various Cas effectors to convert the mRNA information into RNA-guided transcriptional regulation or base editing. We combined the transcription factor-based genetic circuit with the CRISPR system and optimized the genetic switch performance by tuning and processing the gRNA. We then developed a DNA-based recording system for sensing and recording multiplex inflammation markers. These strategies developed here present a simple and robust approach to convert many biological signals into a DNA-based recording system, expanding the toolkit for biotechnological applications. 

Keywords: CRISPR-BE, Genetic circuit, Gut inflammation, DNA recording