Adenosine deaminase acting on RNA 1 (ADAR1) mRNA (ADAR1 mRNA)

Adenosine deaminase acting on RNA 1 (ADAR1) mRNA is the transcript encoding the ADAR1 enzyme, a critical regulator of the innate immune response that catalyzes the conversion of adenosine to inosine (A-to-I editing) in double-stranded RNA (dsRNA) (Source: UniProt P55265). This editing process is essential for distinguishing self-dsRNA from viral dsRNA, thereby preventing the inappropriate activation of the MDA5-MAVS pathway and other sensors like PKR and ZBP1 (Source: PubMed 30111834, 36469491). In many cancers, ADAR1 is overexpressed to suppress the sensing of endogenous dsRNAs, allowing tumors to evade immune detection and resist immunotherapy (Source: Nature 2019, 565(7740):499-503). Targeting ADAR1 mRNA using antisense oligonucleotides (ASOs) or small interfering RNAs (siRNAs) aims to deplete ADAR1 protein levels, which induces a viral mimicry state that sensitizes tumors to immune checkpoint inhibitors (Source: PubMed 33432165). This strategy is particularly promising for cold tumors that do not typically respond to PD-1/PD-L1 blockade. However, therapeutic inhibition of ADAR1 mRNA carries significant risks of systemic autoinflammation and interferonopathies, similar to the symptoms observed in Aicardi-Goutières syndrome (Source: PubMed 25417167). Precise delivery mechanisms or inducible systems may be required to mitigate these safety concerns while maintaining anti-tumor efficacy.

Other names

ADAR mRNADSRAD mRNAG1P1 mRNAIFI4 mRNAK88DSRBP mRNAP117 mRNA

Antisense-mediated mRNA degradation or RNA interference (RNAi) leading to reduced ADAR1 protein expression and subsequent activation of innate immune sensing pathways.