Rational design of lipid and lipid-like structures for non-liver-targeted mRNA therapy

The application of mRNA therapies has witnessed significant advancement since the outbreak of COVID-19. However, the widespread use of mRNA therapies has been restricted by the liver accumulation of traditional lipid structures used as delivery vectors. The efficacy of mRNA expression has been demonstrated to be highly related to vector structures and properties. To expand non-liver organs or cells as therapeutic targets for mRNA, lipid and other lipid-like molecules such as lipid analogs and lipid-like polymers with more favorable mRNA delivery efficiencies have been developed based on a deeper understanding of their structure-function correlations. This review primarily summarizes the structure commonalities leading to an excellent delivery performance and specific organ or cell targeting and illustrates the potential and future prospects of related materials in different biomedical applications of mRNA therapies.