Recent Advances in the Lipid Nanoparticle-Mediated Delivery of mRNA Vaccines

Abstract

In the recent days, lipid nanoparticles have been successfully emerged as one of the most advanced technology for highly efficient in vivo delivery of exogenous mRNA, especially for delivery of COVID-19 vaccines. For the vaccines to be successful or protective, they require highly efficient mRNA delivery systems. However, developing effective, translatable vaccines with better safety against some of the SARS‐CoV‐2 variants is still a challenge. Lipid nanoparticles (LNPs) are composed of four different types of lipids including ionizable lipids, helper or neutral lipids, cholesterol and polyethylene glycol (PEG) attached lipids. In this review, we present recent advancements and insights in designing the advanced LNPs and their composition and properties, with a subsequent discussion on the development of COVID-19 vaccines. In particular, as the ionizable lipids are most important drivers for complexing the mRNA and in vivo delivery, the role of ionizable lipids in mRNA vaccines discussed in detail. Furthermore, the use of LNPs as effective delivery vehicles for vaccination, genome editing, and protein replacement therapy were discussed. Finally, expert opinion of LNPs for mRNA vaccines were discussed which might address the future challenges in the development of mRNA vaccines employing highly efficient LNPs using novel set of ionizable lipids.

Calculating Apparent pKa Values of Ionizable Lipids in Lipid Nanoparticle

“…These statistics represent a remarkable achievement for humanity during society's time of need and these vaccines would not have been possible without the earlier development of LNP delivery systems. As nucleic acid-based therapies, including mRNA, continue to be adapted for new indications and diseases 4,5 , next generation LNP formulations providing more efficient and selective delivery systems are one way to further enable these therapies.…”

Calculating Apparent pKa Values of Ionizable Lipids in Lipid Nanoparticles

“…These statistics represent a remarkable achievement for humanity during society's time of need and these vaccines would not have been possible without the earlier development of LNP delivery systems. As nucleic acid-based therapies, including mRNA, continue to be adapted for new indications and diseases 4,5 , next generation LNP formulations providing more efficient and selective delivery systems are one way to further enable these therapies.…”