Lipid Nanoparticles for the Delivery of mRNA

📖 Top 50% JournalAug 28, 2025Methods in molecular biology (Clifton, N.J.)

Using Tiny Fat Particles to Deliver mRNA

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Abstract

Lipid-based nanoparticles (LNPs) are crucial for the effective delivery of nucleic acids, including mRNA used in COVID-19 vaccines.

Key components of LNPs include ionizable cationic lipids, neutral/helper phospholipids, cholesterol, and lipid-anchored polyethylene glycol.
Ionizable lipids play a significant role in mRNA delivery due to their pH sensitivity and structural variations.
LNPs improve stability, biocompatibility, and delivery efficiency of nucleic acids.
The chapter discusses advancements from traditional lipid carriers to specialized LNP designs that enhance drug delivery.
Recent production techniques for LNPs include microfluidics and impinging-jet mixing, which may improve manufacturing efficiency.

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The development of lipid-based nanoparticles (LNPs) has significantly advanced the field of drug delivery, particularly for nucleic acids, such as mRNA being clinically used in the vaccines against COVID-19. This chapter explores the structural composition and functional properties of LNPs, including key components, such as ionizable cationic lipids, neutral/helper phospholipids, cholesterol, and lipid-anchored polyethylene glycol (PEG) constructs. The discussion includes the role of these components in improving the stability, biocompatibility, and delivery efficiency of LNPs. Special attention is given to the role of ionizable lipids in mRNA delivery, including their pH sensitivity, structural variations, and the implications for endosomal escape and cytosolic release. The chapter also examines the progression from classical lipid carriers to specialized LNP designs, emphasizing the importance of self-assembly properties, preparation methods, and recent advancements in LNP production techniques, including microfluidics, impinging-jet mixing, ethanol dilution, manual mixing, and T-junction blending. The clinical applications of LNPs, particularly in mRNA vaccine development, cancer vaccines, and infectious disease vaccines, are also touched upon.

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