Recent Advances in Site-Specific Lipid Nanoparticles for mRNA Delivery.

The success of mRNA vaccines during the COVID-19 pandemic has greatly accelerated the development of mRNA therapy. mRNA is a negatively charged nucleic acid that serves as a template for protein synthesis in the ribosome. Despite its utility, the instability of mRNA requires suitable carriers for delivery. Lipid nanoparticles (LNPs) are employed to protect mRNA from degradation and enhance its intracellular delivery. To further optimize the therapeutic efficacy of mRNA, site-specific LNPs have been developed. Through local or systemic administration, these site-specific LNPs can accumulate in specific organs, tissues, or cells, allowing for the intracellular delivery of mRNA to specific cells and enabling the exertion of local or systemic therapeutic effects. This not only improves the efficiency of mRNA therapy but also reduces off-target adverse effects. In this review, we summarize recent site-specific mRNA delivery strategies, including different organ- or tissue-specific LNP after local injection, and organ-specific or cell-specific LNP after intravenous injection. We also provide an outlook on the prospects of mRNA therapy.