Ionizable lipids as a promising platform for creating mRNA vaccines

Objectives. Gene therapy involves the administration of various types of therapeutic nucleic acids into the organism, in order to treat severe hereditary diseases, as well as cancer. Furthermore, the COVID-19 pandemic demonstrated the possibility of rapid development and the effectiveness of both DNA and mRNA vaccines for the prevention of viral diseases. Numerous studies in the field of gene therapy have revealed that in most cases successful delivery of nucleic acids requires a special delivery system which protects nucleic acids from the effects of external and internal biological factors. Among the various types of such tools, non-viral delivery systems have proven to be the most versatile and safe ones. In the case of mRNA delivery, such systems are usually called mRNA vaccines, consisting of cationic or ionizable lipids. The purpose of this review is to justify the choice of the optimal structure of lipid components of mRNA vaccines and highlight the current prospects for their clinical use. Results. In this review, we have considered the evolution of lipid structures, from cationic to ionizable, as the main components of mRNA delivery systems. Furthermore, the study demonstrated the necessity to use other types of lipids in mRNA vaccines. It also presents a review of clinical trials of mRNA vaccines against viral and oncological diseases, and provides recommendations for the design of the optimal structure of both cationic and ionizable lipids. Conclusions. The most promising lipids for the development of mRNA vaccines are ionizable. They do not have a permanent positive charge which reduces their cytotoxicity and undesirable binding to components of the immune system. In general, mRNA vaccines can be universal and effective means for treating various types of diseases. However, their composition needs to be careful optimized.