RNA molecules such as messenger RNA（mRNA） for protein complementation and small interfering RNA（siRNA） for gene knockdown have been approved as nucleic acid-based therapeutics. These historical successes will accelerate the innovation of RNA-based medication. In these development, Lipid Nanoparticle（LNP） is making a great contribution as a delivery technology in realizing medical care based on these new modalities. Because of the hydrophilicity and anionic charge of the RNA molecules, plasma/endosomal membrane functions as a biological barrier that interrupts their membrane penetration. An ionizable lipid, the main component of the LNPs, can promote the endosomal escape of the nucleic acids by its membrane destabilization activity in response to the acidic pH. The development of RNA delivery systems is now accelerating to realize a large variety of therapeutics against diseases those were hardly cured by conventionally used small molecule compounds. In this section, the development of current ionizable lipids was summarized from the view point of chemical structure of lipid molecules. As a successful example of mRNA-based therapeutics, current understanding of the RNA vaccine was explained from the viewpoint of vaccine efficacy and mechanism of immune activation. Briefly, LNPs have their own immune-stimulative ability and may establish Th2-biased immunity by themselves. When mRNA or other nucleic acids are loaded, the immune profile will probably change depending on the characteristics of the cargo. On the other hand, empty-LNPs and mRNA-LNPs are considered to promote antibody production through the production of IL-6. However, the cells that produce IL-6, the intra-cellular signaling pathway, and the cell subset responsible for antigen presentation are not yet clear. Understanding these immune-stimulative mechanism will be important for the development of safer and more efficient RNA vaccines and/or mRNA-LNPs for the non-vaccine application. Then, recent advances in the organs/cells specific targeting to control the pharmacokinetics of LNPs were summarized. The properties of mRNA-LNPs such as instability at room temperature are considered to hamper the ligand modification. Further investigation is needed to develop an organ targeting LNPs.