Structure and Function of Cationic and Ionizable Lipids for Nucleic Acid Delivery

Hereditary genetic diseases, cancer, and infectious diseases are affecting global health and become major health issues, but the treatment development remains challenging. Gene therapies using DNA plasmid, RNAi, miRNA, mRNA, and gene editing hold great promise. Lipid nanoparticle (LNP) delivery technology has been a revolutionary development, which has been granted for clinical applications, including mRNA vaccines against SARS-CoV-2 infections. Due to the success of LNP systems, understanding the structure, formulation, and function relationship of the lipid components in LNP systems is crucial for design more effective LNP. Here, we highlight the key considerations for developing an LNP system. The evolution of structure and function of lipids as well as their LNP formulation from the early-stage simple formulations to multi-components LNP and multifunctional ionizable lipids have been discussed. The flexibility and platform nature of LNP enable efficient intracellular delivery of a variety of therapeutic nucleic acids and provide many novel treatment options for the diseases that are previously untreatable.

Automated summary

Hereditary genetic diseases, cancer, and infectious diseases are major health issues, and gene therapies using different techniques show promise for treatment. Lipid nanoparticle (LNP) delivery technology, such as mRNA vaccines, has been successfully used in clinical applications. Understanding the structure, formulation, and function relationship of the lipid components in LNP systems is important for designing more effective LNPs. The flexibility and platform nature of LNP enable efficient intracellular delivery of therapeutic nucleic acids and provide new treatment options for previously untreatable diseases.