Advanced drug delivery reviewsJul 5, 2022

How different fats in tiny particles affect vaccines and gene treatments

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 1, 2026

Abstract

Lipid nanoparticles (LNPs) are crucial for mRNA vaccines and nucleic acid therapies.

LNPs contribute to mRNA vaccine efficacy and the delivery of nucleic acid-based therapies.
The effectiveness of LNPs is influenced by their size, structure, stability, and encapsulation efficiency.
Understanding the role of individual lipid components is essential for improving LNP performance.
Challenges include assessing LNP delivery beyond the liver and evaluating immunogenicity.
Strategies for overcoming these challenges may shape the future of LNP-based therapies.

Simplified

Lipid nanoparticles (LNPs) play an important role in mRNA vaccines against COVID-19. In addition, many preclinical and clinical studies, including the siRNA-LNP product, Onpattro®, highlight that LNPs unlock the potential of nucleic acid-based therapies and vaccines. To understand what is key to the success of LNPs, we need to understand the role of the building blocks that constitute them. In this Review, we discuss what each lipid component adds to the LNP delivery platform in terms of size, structure, stability, apparent pK, nucleic acid encapsulation efficiency, cellular uptake, and endosomal escape. To explore this, we present findings from the liposome field as well as from landmark and recent articles in the LNP literature. We also discuss challenges and strategies related to in vitro/in vivo studies of LNPs based on fluorescence readouts, immunogenicity/reactogenicity, and LNP delivery beyond the liver. How these fundamental challenges are pursued, including what lipid components are added and combined, will likely determine the scope of LNP-based gene therapies and vaccines for treating various diseases. a

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Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

PubMed

How different fats in tiny particles affect vaccines and gene treatments

Abstract

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