(176) Preliminary Development of ”Decoy” Oligodeoxynucleotide-LNPs for NF-κB Inhibition
Introduction: The success of COVID-19 mRNA vaccines has spurred interest in lipid nanoparticles (LNPs) for drug delivery, but a significant challenge is lipid nanoparticle-associated inflammation (LAI). LAI occurs when LNPs damage the endosomal during the process of endosomal escape, activating pro-inflammatory signaling pathways and exacerbating any pre-existing inflammation [1]. Decoy oligonucleotides (ODNs) are a promising option to reduce LAI by binding to the consensus sequence of NF-kB, preventing it from binding to DNA and activating transcription of multiple pro-inflammatory genes [2].
Learning Objectives:
Describe the indicators of LNP-associated inflammation and some of the associated signaling pathways
Explain the effects of structural modifications on ODN efficacy and stability
Evaluate how effectively NF-kB ODN-LNPs reduce LNP-associated inflammation
