mRNA therapeutics deliver a hopeful message.

Graphical abstract Highlights • The production and purification of synthetic mRNA molecules are outlined. • The distinct features of the various synthetic mRNA platforms are present. • Strategies for controlling the inherent innate immunogenicity of synthetic mRNA like the use of innate immune inhibitors are reviewed. • The in vivo delivery of synthetic mRNA, using advanced nanomaterials as well as physical delivery methods, is reviewed. • The therapeutic applications as well as the safety and efficacy of mRNA therapeutics in clinical trials are reviewed. Abstract Messenger RNA based therapeutics have the potential to cause a big revolution in medicine as they can facilitate personalized medicines and allow patients to produce their own therapeutic proteins without the current purification, solubility and inappropriate glycosylation issues associated with recombinant therapeutic proteins. Moreover, a generic and much cheaper production process can be used for mRNA therapeutics as the physicochemical properties of mRNA are independent of its sequence. Furthermore, mRNA vaccines will allow us to respond much quicker to epidemic outbreaks of dangerous infectious diseases as their production is much faster and more flexible than the production of the current vaccines. In the past, the in vivo delivery of mRNA therapeutics was considered as a major bottleneck. However, very recently it has been demonstrated that in vivo delivery issues like low cellular uptake and in vivo degradation by nucleases can be overcome by formulating the therapeutic mRNA into nanoparticles. In this review, we describe the different synthetic mRNA platforms, their production and purification, strategies to tackle the inherent innate immunogenicity of synthetic mRNA, the recent progress in the development of nanoformulations for the in vivo delivery of mRNA, as well as the efficacy and safety of mRNA therapeutics in recent clinical trials. [ABSTRACT FROM AUTHOR]