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 2'-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.