Targeting strategies for mRNA delivery

mRNA gene therapy has recently emerged as a candidate to enable multiple therapeutic applications including protein replacement therapy, vaccine immunology, and regenerative medicine. Despite the extensive therapeutic potential, the successful clinical translation of mRNA gene therapies has been very limited in practice due to the inadequate understanding of how to target various organs or cell type for protein expression. Multiple studies in the past decade have demonstrated carrier material properties and routes of administration as significant parameters influencing the expression profile of mRNA therapeutics. However, the disparate nature of these reports has prevented critical and global understanding of how these factors contribute to organ targeting for mRNA delivery. Elucidation of trends and commonalities in materials achieving tissue specific mRNA delivery may enable the realization of the medical and commercial promise of therapeutic mRNA medicines. The purpose of this review is to provide a thorough and robust meta-analysis of the various materials that have been successfully used to target different organs for mRNA delivery. The article summarizes the distinct properties of the materials used as well as evaluates various routes of administration of mRNA therapeutics and the applications that can be achieved. This review will therefore serve as useful guide for the community in the development of future materials for mRNA delivery to enable the full potential of this nucleic acid modality for gene therapy.