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Transcription factor p65 (RELA) messenger RNA encodes the p65 subunit of the NF-kappa-B (NF-κB) complex, which serves as a master regulator of the immune system and inflammatory responses (UniProt: P19838). The p65 subunit is a member of the Rel family and contains a transactivation domain necessary for the transcriptional activity of the canonical NF-κB pathway (NCBI Gene: 5970). Overexpression or constitutive activation of the NF-κB pathway, often driven by RELA, is a hallmark of many cancers and chronic inflammatory conditions, where it promotes cell survival, proliferation, and the production of pro-inflammatory cytokines (PubMed: 31435140). Targeting the mRNA directly using small interfering RNA (siRNA) or antisense oligonucleotides (ASOs) allows for the knockdown of p65 protein synthesis, providing a more specific therapeutic intervention than broad-spectrum NF-κB inhibitors (PubMed: 25614320). This strategy is being explored to sensitize tumor cells to apoptosis and to treat autoimmune disorders by dampening pathological inflammation (PubMed: 12060563). However, therapeutic success depends on overcoming challenges such as efficient intracellular delivery and avoiding the activation of the innate immune system by the therapeutic nucleic acids themselves.
RNA interference (RNAi) or antisense-mediated degradation of RELA mRNA, leading to reduced p65 protein expression and inhibition of NF-kappa-B signaling.
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