Nanomedicines to Deliver mRNA: State of the Art and Future Perspectives

Abstract

The use of messenger RNA (mRNA) in gene therapy is increasing in recent years, due to its unique features compared to plasmid DNA: Transient expression, no need to enter into the nucleus and no risk of insertional mutagenesis. Nevertheless, the clinical application of mRNA as a therapeutic tool is limited by its instability and ability to activate immune responses; hence, mRNA chemical modifications together with the design of suitable vehicles result essential. This manuscript includes a revision of the strategies employed to enhance in vitro transcribed (IVT) mRNA functionality and efficacy, including the optimization of its stability and translational efficiency, as well as the regulation of its immunostimulatory properties. An overview of the nanosystems designed to protect the mRNA and to overcome the intra and extracellular barriers for successful delivery is also included. Finally, the present and future applications of mRNA nanomedicines for immunization against infectious diseases and cancer, protein replacement, gene editing, and regenerative medicine are highlighted.

Nanomaterial Delivery Systems for mRNA Vaccines

“…The purpose of this review is to overview the development of delivery systems for mRNA and then to summarize the preclinical and clinical findings of the SARS-CoV-2 mRNA vaccines and relate them to characteristics of the delivery system that contribute to their success. Several excellent reviews of mRNA delivery systems for vaccines and therapeutics that predate COVID-19 have been recently published [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ].…”

Paving the Road for RNA Therapeutics

“…As discussed here, advances in nucleic acid chemistry combined with suitable delivery vehicles boosted the field, and these efforts eventually crystalized into the approval of the first siRNA-based drug, patisiran in 2018 [ 15 ]. Since then, the field of RNA therapeutics has received a boost, and this is evident when looking at the clinical pipeline that contains a wide range of RNA therapeutics at all stages of clinical development for a variety of medical conditions [ 34 , 93 ] ( Table 1 ).…”

mRNA technology as one of the promising platforms for the SARS-CoV-2 vaccine development

“…To perform its task, the mRNA must enter the cell's cytoplasm where the protein encoded by it can be translated. A range of mRNA delivery methods have been described, including administration of the vaccine by elec troporation, injection into muscles, lymph nodes, or directly into organs, or administration intranasally, rectally, or orally (GómezAguado et al, 2020;Wadhwa et al, 2020). Messenger RNA vaccination is also hindered by its degradation by various extracellular ribonucleases, which are abundant in tissues and in the intercellular space (Houseley, Tollervey, 2009).…”