Adenosine deaminase acting on RNA 1 and 2 (ADAR1/ADAR2)

Adenosine deaminases acting on RNA 1 and 2 (ADAR1 and ADAR2) are enzymes that catalyze the hydrolytic deamination of adenosine to inosine (A-to-I editing) in double-stranded RNA (dsRNA). ADAR1 is a critical regulator of the innate immune system, where it edits endogenous dsRNAs to prevent them from triggering cytosolic sensors like MDA5, which would otherwise initiate a type I interferon response. ADAR2 is predominantly expressed in the nervous system and is essential for the site-specific recoding of mRNAs, most notably the glutamate receptor subunit GRIA2, which is vital for preventing excitotoxicity. In the context of drug development, ADAR1 is being pursued as a high-priority immuno-oncology target; its inhibition can overcome resistance to checkpoint inhibitors by inducing a viral mimicry state that activates anti-tumor immunity. However, therapeutic intervention must carefully manage the risk of inducing autoinflammatory conditions, such as Aicardi-Goutières syndrome, or causing neurological dysfunction through the unintended inhibition of ADAR2-mediated editing.

Other names

ADARADARB1DSRADRED1DRADADRADA2G1P1IFI4K88DSRBPA-to-I RNA editing enzymes

Inhibition of adenosine-to-inosine (A-to-I) deamination in double-stranded RNA (dsRNA), leading to the accumulation of unedited dsRNA which activates innate immune sensing pathways (e.g., MDA5-MAVS) and induces type I interferons.