Methylation of DNA duplexes regulates cGAS-mediated innate immune activation via condensate formation

Abstract

Exogenous DNA activates innate immunity via the cGAS–STING pathway, but the impact of chemical modifications has not been investigated sufficiently. Here, we show that DNA duplexes containing 2ʹ-O-methyl ribonucleotides enhance cGAS-driven liquid–liquid phase separation and enzymatic activity, function effectively in DNA nanotherapeutics in living cells, and enable the rational control of innate immune signaling.