Lipid nanoparticles: A delicate nucleic acid delivery system to be further explored

Breakthroughs in delivery systems are critical to the development of emerging nucleic acid drugs and vaccines. Lipid nanoparticles (LNPs) are currently the only carriers approved for siRNA and mRNA delivery in the clinic. The success of LNPs relies on decades of iterative research to make them safe, stable and highly efficient for nucleic acids delivery in vivo. The beauty of LNP includes the simple formulation, adjustable compositions and easy of manufacture, but actually it's a very delicate system with complicated structures and sensitive effectiveness. While it is considered to be the most well-studied nucleic acids delivery system, the robust function and application potential of LNPs are far from being fully explored. In this review, we summarized the historical development of the most classic LNPs accompany with a systemic analysis of the critical factors that affect delivery efficiency. The debated LNP structure with different hypotheses and possible delivery mechanisms of LNPs are further discussed. We also enumerated recent major advances in using LNPs for nucleic acid delivery especially focused on the mRNA applications. The ongoing development of LNPs not only harbors immense potential but also imparts valuable insights that can inform the evolution of delivery systems for nucleic acids. © 2024