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

Abstract

Lipid nanoparticles (LNPs) have recently emerged as one of the most advanced technologies for the highly efficient in vivo delivery of exogenous mRNA, particularly for COVID-19 vaccine delivery. LNPs comprise four different lipids: ionizable lipids, helper or neutral lipids, cholesterol, and lipids attached to polyethylene glycol (PEG). In this review, we present recent the advances and insights for the design of LNPs, as well as their composition and properties, with a subsequent discussion on the development of COVID-19 vaccines. In particular, as ionizable lipids are the most critical drivers for complexing the mRNA and in vivo delivery, the role of ionizable lipids in mRNA vaccines is discussed in detail. Furthermore, the use of LNPs as effective delivery vehicles for vaccination, genome editing, and protein replacement therapy is explained. Finally, expert opinion on LNPs for mRNA vaccines is discussed, which may address future challenges in developing mRNA vaccines using highly efficient LNPs based on a novel set of ionizable lipids. Developing highly efficient mRNA delivery systems for vaccines with improved safety against some severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants remains difficult.

A Journey of Challenges and Victories: A Bibliometric Worldview of Nanomedicine since the 21st Century

“…LNPs typically exhibit a spherical morphology, characterized by a lipid bilayer enveloping an aqueous core, and are commonly comprised of four essential lipids: pH‐responsive ionizable cationic lipids, helper lipids, cholesterol, and polyethylene glycol (PEG)‐conjugated lipids. [ 178 ] Unadorned mRNA possesses a substantial molecular weight (10 4 –10 6 Da), bears a negative charge, encounters challenges in traversing cellular membranes, and is prone to degradation by ribonucleases. LNPs‐encapsulated mRNA enters the cell through endocytosis and subsequently forms endosomes.…”

“…[ 184,185 ] Lipid‐anchored PEG constructs act as anchors within LNPs, preventing biocleavage, enhancing colloidal stability, and extending the half‐life. [ 178,186 ]…”

“…[184,185] Lipidanchored PEG constructs act as anchors within LNPs, preventing biocleavage, enhancing colloidal stability, and extending the half-life. [178,186] It is crucial to acknowledge that mRNA-LNPs vaccines have demonstrated significant transformative and successful outcomes in practical applications. Nevertheless, clinical practice has highlighted several noteworthy concerns, with the primary and most prominent being the difficulties associated with storing and transporting these vaccines under ultra-low-temperature freezing conditions.…”

In Situ Reprogramming of Immune Cells Using Synthetic Nanomaterials

“…[31] Synthetic nanomaterials, such as lipid nanoparticles (LNPs) and polymers, might be promising alternatives to viral vectors owing to their minimal immunogenicity, ease of scale-up production as well as low costs. [32][33][34] Moreover, it is also worth noting that synthetic nanomaterials have the probable advantage of a more defined regulatory pathway in the light of the approvals of COVID-19 mRNA vaccines (Comirnaty and Spikevax) using LNP formulations by the FDA. In addition, mounting evidence demonstrates that synthetic nanomaterials can be flexibly constructed with diverse ligand modifications (antibody, peptide, etc.)…”

Combinatorial Screening of Biscarbamate Ionizable Lipids Identifies a Low Reactogenicity Lipid for Lipid Nanoparticle mRNA Delivery

“…mRNA-based products hold tremendous therapeutic potential as vaccines against infectious diseases and for protein replacement, gene editing, and cancer immunotherapy. [1][2][3] In all cases, the patient's own cellular machinery is utilized as the workforce to produce therapeutic proteins. Key to the successful deployment of mRNA drugs is the delivery of intact mRNA into the cytoplasm of cells where it can be efficiently translated by ribosomes.…”