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Tumor necrosis factor alpha messenger RNA (TNFα mRNA)

Target
TNFα mRNA
Molecular classification
Nucleic acid, Messenger RNA
01

Overview

Tumor necrosis factor alpha (TNFα) messenger RNA is the ribonucleic acid transcript that serves as the template for the synthesis of the TNFα protein, a central mediator of the mammalian immune response. Produced primarily by activated macrophages and T-cells, this mRNA is rapidly upregulated in response to inflammatory stimuli, leading to the secretion of the pro-inflammatory TNFα cytokine (PubMed: 16461134). Overexpression or dysregulation of TNFα mRNA is a primary driver in the pathogenesis of chronic autoimmune disorders such as rheumatoid arthritis and inflammatory bowel disease (NIH: PMC3092143). By targeting the mRNA transcript using antisense oligonucleotides (ASOs) or small interfering RNAs (siRNAs), therapeutic interventions aim to silence the production of the cytokine at the pre-translational level. This approach offers a distinct mechanism compared to monoclonal antibodies, which target the circulating protein, potentially allowing for more localized or sustained suppression of inflammation. Current research focuses on improving the delivery of these nucleic acid-based drugs to specific immune cells while minimizing systemic off-target effects.

Other names
TNF-alpha mRNATNFA mRNACachectin mRNATumor necrosis factor messenger RNATNF-α transcript
02

Mechanism of action

Antisense-mediated degradation via RNase H, RNA interference (RNAi) via the RISC complex, or translation inhibition to prevent the synthesis of the TNFα protein.

03

Biological functions

Protein synthesis templateImmune response regulationPro-inflammatory signalingRegulation of apoptosisAcute phase reaction induction
04

Disease associations

Rheumatoid arthritisCrohn's diseaseUlcerative colitisPsoriasisAnkylosing spondylitisSeptic shockCancer-associated cachexia
05

Safety considerations

Off-target RNA bindingImmunogenicity of delivery vehicles (e.g., lipid nanoparticles)Increased risk of opportunistic infectionsInjection site or infusion reactionsPotential for hepatotoxicity with certain oligonucleotide chemistries
06

Interacting drugs

ISIS 104838

3 more in the full profile.

07

Biomarkers

Serum TNFα protein levelsC-reactive protein (CRP)Erythrocyte sedimentation rate (ESR)TNFα mRNA expression in PBMCs

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