Materials for non-viral intracellular delivery of messenger RNA therapeutics

Though therapeutics based on messenger RNA (mRNA) have broad potential in applications such as protein replacement therapy, cancer immunotherapy, and genomic engineering, their effective intracellular delivery remains a challenge. A chemically diverse suite of delivery materials with origins as materials for cellular transfection of DNA and small interfering RNAs (siRNAs) has recently been reported to have promise as non-viral delivery agents for mRNA. These materials include covalent conjugates, protamine complexes, nanoparticles based on lipids or polymers, and hybrid formulations. This review will highlight the use of delivery materials for mRNA, with a specific focus on their mechanisms of action, routes of administration, and dosages. Additionally, strategies in which these materials can be adapted and optimized to address challenges specific to mRNA delivery are also discussed. The technologies included have shown varying promise for therapeutic use, specifically having been used to deliver mRNA in vivo or exhibiting characteristics that could make in vivo use a possibility. In so doing, it is the intention of this review to provide a comprehensive look at the progress and possibilities in applying nucleic acid delivery technology specifically toward the emerging area of mRNA therapeutics.