Nanotechnologies in delivery of mRNA therapeutics using nonviral vector-based delivery systems

Because of its safe and effective protein expression profile, in vitro transcribed messenger RNA (IVT-mRNA) represents a promising candidate in the development of novel therapeutics for genetic diseases, vaccines or gene editing strategies, especially when its inherent shortcomings (for example, instability and immunogenicity) have been partially addressed via structural modifications. However, numerous unsolved technical difficulties in successful in vivo delivery of IVT-mRNA have greatly hindered the applications of IVT-mRNA in clinical development. Recent advances in nanotechnology and material science have yielded many promising nonviral delivery systems, some of which were able to efficiently facilitate targeted in vivo delivery of IVT-mRNA in safe and noninvasive manners. The diversity and flexibility of these delivery systems highlight the recent progress of IVT-mRNA-based therapy using nonviral vectors. In this review, we summarize recent advances of existing and emerging nonviral vector-based nanotechnologies for IVT-mRNA delivery and briefly summarize the interesting but rarely discussed applications on simultaneous delivery of IVT-mRNA with DNA.