IFN-alpha 21

Interferon alpha-21 (IFN-α21, gene IFNA21, formerly IFN-αC) is a human type I interferon subtype lying in the chromosome 9p22 interferon cluster. The mature cytokine is 166 amino acids long and, engaging the shared IFNAR1/IFNAR2 receptor, activates the canonical JAK-STAT1/2-IRF9 axis to induce antiviral ISGs, upregulate MHC class I and modulate immune cell function. IFN-α21 has attracted pharmacological attention because subtype comparisons consistently rank it among the IFN-α variants with superior specific antiviral and antiproliferative activity coupled with favorable receptor-activation profiles. Consequently, engineered and pegylated forms of IFN-α21 were explored as next-generation therapeutics; notably, pegylated IFN-α21 variants have been evaluated clinically for chronic hepatitis C with the aim of improving upon the tolerability of pegylated IFN-α2a/2b. Beyond therapy, IFNA21 expression contributes to the endogenous interferon response of leukocytes during viral infection, and its gene shows regulatory polymorphisms influencing circulating interferon levels.