Immune response to the components of lipid nanoparticles for ribonucleic acid therapeutics

Ribonucleic acid therapeutics have advantages over biologics and small molecules, including lower safety risks, cheaper costs, and extensive targeting flexibility, which is rapidly fueling the expansion of the field. This is made possible by breakthroughs in the field of drug delivery, wherein lipid nanoparticles (LNPs) are one of the most clinically advanced systems. LNP formulations that are currently approved for clinical use typically contain an ionizable cationic lipid, a phospholipid, cholesterol, and a polyethylene glycol-lipid; each contributes to the stability and/or effectiveness of LNPs. In this review, we discuss the immunomodulatory effects associated with each of the lipid components. We highlight several studies in which the components of LNPs have been implicated in cellular sensing and explore the pathways involved.