Decoy oligonucleotides targeting NF-κB: a promising therapeutic approach for inflammatory diseases.

Abstract

Nuclear factor-kappa B (NF-κB) transcription factor plays a crucial function in controlling several cellular processes, including the production of inflammatory mediators. The aberrant activation of this transcription factor and its signaling pathway is associated with the pathophysiology of many diseases. Therefore, discovering drugs that target NF-κB is crucial for treating various diseases. Decoy oligonucleotides (decoy ONs) are a pharmacological approach that specifically inhibits NF-κB activation and are used to treat several inflammatory diseases. Decoys that target NF-κB have been shown to enhance radiosensitivity and drug sensitivity in vitro and strongly block IL-6 and IL-8 gene expression induced by TNF-α in experimental cell systems. In vivo, NF-κB decoy reduced atherosclerotic plaque, prevented atopic dermatitis and extended cardiac transplant survival. Decoys have the potential to be used in clinical applications, but they face several challenges. To overcome these limitations, researchers have conducted studies on chemical modifications and delivery techniques. Innovative compounds that target NF-κB, such as NF-κB-decoy-based sensor-containing models, phosphorothioate hairpin-modified oligonucleotides, and peptide nucleic acid (PNA)-based transcription factor decoys, are very attractive. This research aims to explore the use of decoys to combat NF-κB in various disorders.