Interaction design in mRNA delivery systems

Following the coronavirus disease 2019 (COVID-19) pandemic, mRNA technology has made significant breakthroughs, emerging as a potential universal platform for combating various diseases. To address the challenges associated with mRNA delivery, such as instability and limited delivery efficacy, continuous advancements in genetic engineering and nanotechnology have led to the exploration and refinement of various mRNA structural modifications and delivery platforms. These achievements have significantly broadened the clinical applications of mRNA therapies. Despite the progress, the understanding of the interactions in mRNA delivery systems remains limited. These interactions are complex and multi-dimensional, occurring between mRNA and vehicles as well as delivery materials and helper ingredients. Resultantly, stability of the mRNA delivery systems and their delivery efficiency can be both significantly affected. This review outlines the current state of mRNA delivery strategies and summarizes the interactions in mRNA delivery systems. The interactions include the electrostatic interactions, hydrophobic interactions, hydrogen bonding, π-π stacking, coordination interactions, and so on. This interaction understanding provides guideline for future design of next-generation mRNA delivery systems, thereby offering new perspectives and strategies for developing diverse mRNA therapeutics.