Indoleamine 2,3-dioxygenase 1 mRNA (IDO1 mRNA)

Indoleamine 2,3-dioxygenase 1 (IDO1) mRNA is the transcript encoding the IDO1 enzyme, a critical immunometabolic regulator that catalyzes the rate-limiting step of tryptophan degradation into kynurenine (PubMed: 26611904). In the tumor microenvironment, IDO1 mRNA is often upregulated by interferon-gamma, leading to high protein levels that suppress T-cell activity and promote immune evasion (PubMed: 35003126). Therapeutic strategies targeting IDO1 mRNA include antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) designed to silence the gene and prevent the production of the immunosuppressive enzyme (PubMed: 19147749). Additionally, mRNA-based vaccines like Moderna's mRNA-4359 utilize IDO1 sequences to stimulate an immune response against IDO1-expressing tumor and suppressor cells (Moderna, 2024). By reducing IDO1 activity, these therapies aim to restore local tryptophan levels and decrease toxic kynurenine metabolites, thereby reactivating anti-tumor immunity. While small molecule inhibitors of the IDO1 protein have faced clinical setbacks, mRNA-targeted and mRNA-encoded strategies represent a novel frontier in restoring anti-tumor immunity.

Other names

IDO1IDOINDOIndoleamine-pyrrole 2,3-dioxygenase 1

Antisense-mediated mRNA degradation, RNA interference (RNAi), and encoding of antigenic epitopes for immune stimulation.