Fluorescent Biosensor for Cyclic GMP-AMP (cGAMP)

The cGAS-cGAMP-STING pathway is an important immune surveillance pathway which gets activated in presence of cytoplasmic DNA either due to a microbial infection or a patho-physiological condition, including cancer and autoimmune disorders. Sensing 2’3’ cGAMP level is important in diagnostics perspective as well as in basic understanding of their regulation. Small molecule activators of this pathway have also been shown to activate an anti-cancer immune response and thus an important use for pharmaceutical applications. However, a high throughput method to screen for such potential drugs is still not available. UC Berkeley researchers have designed a RNA-based fluorescent biosensor for directly detecting 2’3’ cGAMP. The biosensor was able to detect 2’3’ cGAMP and assay cGAS activity in vitro and thus would be useful for high throughput screening of small molecule modulators of cGAS activity. The biosensor was sensitive enough to quantify 2’3’ cGAMP in dsDNA- stimulated mammalian cell extracts. Terri Sale terri.sale@berkeley.edu 510-643-4219