Interleukin 33 messenger RNA (IL33 mRNA) (IL33 mRNA)

Interleukin 33 (IL-33) messenger RNA (mRNA) is the genetic template for the IL-33 protein, a potent pro-inflammatory cytokine and member of the IL-1 superfamily (Cayrol & Girard, 2014). IL-33 functions as an alarmin, constitutively expressed in the nuclei of epithelial and endothelial cells and released upon tissue damage to trigger innate and adaptive immune responses via the ST2 receptor (Liew et al., 2016). Targeting the IL-33 mRNA transcript allows for the modulation of IL-33 levels at the pre-translational stage, potentially preventing the downstream inflammatory cascade associated with chronic conditions such as asthma, atopic dermatitis, and chronic obstructive pulmonary disease (COPD) (Chan et al., 2019). Therapeutic strategies focusing on IL-33 mRNA typically involve the use of antisense oligonucleotides (ASOs) or small interfering RNAs (siRNAs) designed to induce RNase H-mediated degradation or RNA interference, respectively (Crooke et al., 2018). This approach is being explored to overcome the limitations of monoclonal antibodies, such as high dosing requirements and the challenge of neutralizing intracellular IL-33 pools. However, successful clinical application requires overcoming delivery barriers to specific tissues and minimizing non-specific immune activation by the therapeutic nucleic acids (Khvorova & Watts, 2017).

Other names

IL-33 mRNANuclear factor from high endothelial venules mRNANF-HEV mRNADVS27 mRNAC9orf26 mRNAInterleukin-33 transcript

RNase H-mediated degradation of mRNA or RNA interference (RNAi) to prevent translation of the IL-33 protein.