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Review
. 2022 Feb:73:329-336.
doi: 10.1016/j.copbio.2021.09.016. Epub 2021 Oct 26.

Principles for designing an optimal mRNA lipid nanoparticle vaccine

Edo Kon  1 , Uri Elia  2 , Dan Peer  3
Affiliations
Review

Principles for designing an optimal mRNA lipid nanoparticle vaccine

Edo Kon et al. Curr Opin Biotechnol. 2022 Feb.

Abstract

mRNA Lipid nanoparticles (LNPs) have recently been propelled onto the center stage of therapeutic platforms due to the success of the SARS-CoV-2 mRNA LNP vaccines (mRNA-1273 and BNT162b2), with billions of mRNA vaccine doses already shipped worldwide. While mRNA vaccines seem like an overnight success to some, they are in fact a result of decades of scientific research. The advantage of mRNA-LNP vaccines lies in the modularity of the platform and the rapid manufacturing capabilities. However, there is a multitude of choices to be made when designing an optimal mRNA-LNP vaccine regarding efficacy, stability and toxicity. Herein, we provide a brief on what we consider to be the most important aspects to cover when designing mRNA-LNPs from what is currently known and how to optimize them. Lastly, we give our perspective on which of these aspects is most crucial and what we believe are the next steps required to advance the field.

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Figures

None
Graphical abstract
Figure 1
Figure 1
Optimizing mRNA sequence and modifications for mRNA-LNP vaccines. A scheme representing the mRNA construct elements to consider when designing an mRNA-LNP vaccine.
Figure 2
Figure 2
LNP formulation considerations. (a) A scheme representing the elements of the ionizable lipid. (b) Chemical structures of the three clinically approved ionizable lipids. ALC-0315 (Pfizer/BioNtech’s BNT162b), SM-102 (Moderna’s SM-102) and Dlin-MC3-DMA (siRNA LNPs — Alnylam’s Patisiran) [34].
See this image and copyright information in PMC

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