Adenosine deaminase acting on RNA (ADAR) (ADAR)

Adenosine deaminase acting on RNA (ADAR) enzymes are a family of proteins, including ADAR1, ADAR2, and ADAR3, that catalyze the post-transcriptional deamination of adenosine to inosine (A-to-I) in double-stranded RNA (dsRNA) [1, 2]. This RNA editing process is essential for maintaining cellular homeostasis by preventing the innate immune system, specifically the MDA5 receptor, from erroneously sensing endogenous dsRNA as viral infection [3, 5]. ADAR1 is ubiquitously expressed and plays a critical role in immune regulation, while ADAR2 is primarily active in the brain, where it edits transcripts encoding neurotransmitter receptors [2, 4]. In the context of drug development, ADAR1 is a high-priority target in oncology; its inhibition can overcome resistance to immune checkpoint blockers by inducing a viral mimicry state that activates anti-tumor immunity [6, 7]. Additionally, endogenous ADAR enzymes are being utilized as therapeutic tools through the use of site-directed RNA editing oligonucleotides, which recruit the enzyme to correct pathogenic point mutations in mRNA [8, 10]. This approach offers a potentially safer and more transient alternative to DNA-based gene editing for treating genetic diseases like Alpha-1 antitrypsin deficiency [8, 9].

Other names

ADAR1ADAR2ADAR3ADARB1ADARB2Double-stranded RNA-specific adenosine deaminaseRNA-specific adenosine deaminaseDSRADK88DSRBPDRADA

Recruitment of endogenous ADAR enzymes to catalyze site-specific adenosine-to-inosine (A-to-I) editing of mRNA [8, 9]; Small molecule inhibition of ADAR1 to activate the MDA5-mediated innate immune response in the tumor microenvironment [6, 7].