REVIEW ON: MRNA DELIVERY VIA LIPID NANOPARTICALS

Messenger RNA (mRNA) has emerged as a transformative tool in modern biomedical science, capable of directing cells to produce therapeutic proteins and vaccines. However, its clinical potential was long constrained by instability, rapid degradation by nucleases, and inefficient cellular uptake. The advent of lipid nanoparticle (LNP) delivery systems revolutionized this landscape, offering a biocompatible and efficient platform to encapsulate, protect, and deliver mRNA into target cells. This review outlines the fundamental principles, evolution, mechanisms, advantages, limitations, and future prospects of mRNA delivery via lipid nanoparticles. The discovery of mRNA in the early 1960s laid the foundation for molecular biology, yet decades of research were required to overcome the challenges of mRNA degradation and immunogenicity. In the 1990s, lipid-based carriers were proposed as potential delivery vehicles, and by the 2000s, major breakthroughs such as chemical modification of nucleosides and the development of ionizable lipids-enabled safe and effective delivery. These advances culminated in the unprecedented success of mRNA-LNP vaccines during the COVID-19 pandemic, proving the platform's clinical efficacy and scalability. Structurally, LNPs are composed of four major lipid components-ionizable, lipids, helper lipids (phospholipids), cholesterol, and polyethylene glycol (PEG)-lipids. Ionizable lipids play a key role in mRNA encapsulation and endosomal escape by altering their charge in response to pH changes. Helper lipids stabilize the bilayer structure, cholesterol enhances rigidity and strength, while PEG-lipids improve circulation time and prevent aggregation.