Cyclic GMP-AMP synthase mRNA (cGAS mRNA)

Cyclic GMP-AMP synthase (cGAS) mRNA is the messenger RNA transcript that encodes the cGAS enzyme, a primary sensor of cytosolic double-stranded DNA (dsDNA) in mammalian cells (Sun et al., 2013, Science). The protein product of this mRNA is responsible for synthesizing the second messenger cyclic GMP-AMP (cGAMP), which subsequently activates the Stimulator of Interferon Genes (STING) protein to trigger a type I interferon response (Ablasser et al., 2013, Nature). Targeting cGAS mRNA is an emerging therapeutic approach for treating autoimmune and autoinflammatory diseases where the cGAS-STING pathway is chronically overactive due to the presence of self-DNA in the cytoplasm, such as in Aicardi-Goutières syndrome or systemic lupus erythematosus (Rice et al., 2014, Nature Genetics). Therapeutic modalities like small interfering RNAs (siRNAs) or antisense oligonucleotides (ASOs) are designed to bind specifically to the cGAS mRNA sequence, leading to its degradation and a subsequent reduction in cGAS protein levels (Volkman et al., 2019, Immunity). This strategy aims to dampen the pathological immune signaling at its source, providing a highly specific alternative to broad immunosuppressants or small molecule inhibitors of the cGAS enzyme itself. By modulating the levels of the transcript, researchers hope to achieve precise control over the innate immune response in various inflammatory contexts.

Other names

MB21D1 mRNAC6orf150 mRNACyclic GAS mRNAh-cGAS mRNA

RNA interference (RNAi) or antisense oligonucleotide (ASO) mediated degradation of the mRNA transcript to prevent translation into the cGAS protein.