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.
Highlights
Nano-Oncology and Translational Therapeutics Group, Health Research Institute of Santiago de Compostela (IDIS), SERGAS, 15706 Santiago de Compostela, Spain
The development and commercialization of Messenger RNA (mRNA) COVID-19 vaccines have pivoted the way towards future applications of mRNA medicines by finding a solution to the problem of delivery
It is clear that the full potential of mRNA therapeutics, along with its advantages could not be envisioned without nanomedicine
Summary
The first isolation of messenger RNA (mRNA) was published in Nature in 1961 [1,2], starting the path towards a full understanding of this molecule [3]. MRNA sequences can be modified and updated, which is an important fact to consider in vaccinology (i.e., when mutations of the target protein occur) These advantages are important when comparing mRNA technology to protein delivery technology, which normally comes with short half-lives and expensive and tedious industrial processes [4–6]. Naked mRNA is not capable of crossing lipid bilayers to reach its target To overcome these limitations and to improve the pharmacokinetic and pharmacodynamic properties of naked mRNA, two main strategies have been proposed to date: the introduction of chemical modifications on the sequence and the use of a delivery vehicle, which will be discussed in more detail
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