The Potential of Nanomedicine to Unlock the Limitless Applications of mRNA

Abstract

The year 2020 was a turning point in the way society perceives science. Messenger RNA (mRNA) technology finally showed and shared its potential, starting a new era in medicine. However, there is no doubt that commercialization of these vaccines would not have been possible without nanotechnology, which has finally answered the long-term question of how to deliver mRNA in vivo. The aim of this review is to showcase the importance of this scientific milestone for the development of additional mRNA therapeutics. Firstly, we provide a full description of the marketed vaccine formulations and disclose LNPs’ pharmaceutical properties, including composition, structure, and manufacturing considerations Additionally, we review different types of lipid-based delivery technologies currently in preclinical and clinical development, namely lipoplexes and cationic nanoemulsions. Finally, we highlight the most promising clinical applications of mRNA in different fields such as vaccinology, immuno-oncology, gene therapy for rare genetic diseases and gene editing using CRISPR Cas9.

mRNA vaccines: a new opportunity for malaria, tuberculosis and HIV

“…However, the positively charged cationic lipids tend to aggregate with negatively charges serum proteins, increasing the clearance rate, and have a cytotoxic effect, limiting their clinical applications (35,38). Incorporation of hydrophilic polymers such as polyethylene glycol (PEG) reduces the toxicity of cationic liposomes but can generate anti-PEG antibodies upon repeated administrations, increasing their clearance rate (39).…”

A Triazolium‐Anchored Self‐Immolative Linker Enables Self‐Assembly‐Driven siRNA Binding and Esterase‐Induced Release

“…In particular, the nature of the ionizable lipid has been optimized to greatly improve their delivery efficacy through an enhancement in endosomal escape -two-armed cylindrical or inverted cone structures with packing parameter greater than 1/2 being a must. [24][25][26][27] However, these multi-component formulations must be preserved at (ultra)low temperatures for storage and distribution to preserve their structure (current limit of 1-3 months at 2-8 °C for the mRNA Covid-19 vaccines [28,29] ). Therefore, a current challenge in the field is to make these lipid nanoparticles more stable while keeping their dynamic nature which is key to deliver the nucleic acid payload.…”

“…However, these multi‐component formulations must be preserved at (ultra)low temperatures for storage and distribution to preserve their structure (current limit of 1–3 months at 2–8 °C for the mRNA Covid‐19 vaccines[ 28 , 29 ]). Therefore, a current challenge in the field is to make these lipid nanoparticles more stable while keeping their dynamic nature which is key to deliver the nucleic acid payload.…”

Deagglomeration of DNA nanomedicine carriers using controlled ultrasonication

“…The use of particle-based systems as delivery vehicles have shown potential for protecting these fragile biopolymers, while at the same time enabling their delivery to the targeted site. Proposed particle platforms for the delivery of oligonucleotides [1] , [2] , [3] include protein constructs such as virus-based and virus-like particles, polymer particles [4] , [5] , [6] , [7] , lipid-based particles such as liposomes and lipid-based nanoparticles [8] , [9] and inorganic particles. The most common inorganic carriers under development include silica nanoparticles [10] , [11] , [12] , gold nanoparticles [13] and magnetic nanoparticles [14] , but carbon nanotubes, graphene and quantum dots have also been proposed [15] , [16] , [17] .…”