Gasdermin D mRNA (GSDMD mRNA)

Gasdermin D (GSDMD) mRNA is the transcript encoding the executioner protein of pyroptosis, a highly inflammatory form of programmed cell death. Upon translation, the GSDMD protein is cleaved by inflammatory caspases (such as Caspase-1 or Caspase-4/5/11), releasing an N-terminal fragment that oligomerizes to form large pores in the plasma membrane. These pores facilitate the release of pro-inflammatory cytokines like IL-1β and IL-18 and eventually lead to cell lysis. Targeting GSDMD at the mRNA level using antisense oligonucleotides (ASOs) or small interfering RNAs (siRNAs) aims to deplete the cellular pool of GSDMD protein, thereby preventing pore formation and the subsequent hyper-inflammatory response. This approach is particularly relevant in treating conditions characterized by cytokine storms, such as sepsis, and chronic inflammatory diseases like gout or multiple sclerosis. While protein-level inhibitors exist, mRNA-targeting strategies offer high specificity and the potential for long-lasting suppression of the pyroptotic pathway.

Other names

Gasdermin-D mRNADF5L mRNAGSDMD transcriptGasdermin domain-containing protein 1 mRNA

RNA interference (siRNA) or RNase H-mediated degradation (ASO) to prevent the translation of Gasdermin D protein, thereby inhibiting the formation of membrane pores and the execution of pyroptosis.