Development of a Ready-to-Use-Type RNA Vaccine Carrier Based on an Intracellular Environment-Responsive Lipid-like Material with Immune-Activating Vitamin E Scaffolds

• Published in: Pharmaceutics Vol. 15; no. 12; p. 2702
• Main Authors: Anindita, Jessica, Tanaka, Hiroki, Oyama, Ryotaro, Hagiwara, Shinya, Shirane, Daiki, Taneichi, Sakura, Nakai, Yuta, Tange, Kota, Hatakeyama, Hiroto, Sakurai, Yu, Akita, Hidetaka
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 29.11.2023; MDPI
• Subjects: Antigens; Cells; Chemical bonds; Cytoplasm; Drug delivery systems; Drugs; Experiments; freeze-drying; Laboratory animals; lipid nanoparticle; Lipids; Messenger RNA; mRNA vaccine; Penicillin; Pharmaceutical industry; Proteins; Scientific equipment and supplies industry; Vaccines; Vehicles; Vitamin E; United States; Massachusetts; Japan; England; St Louis Missouri; United Kingdom > UK; United States > US; freeze-drying; lipid nanoparticle; mRNA vaccine
• ISSN: 1999-4923; 1999-4923
• DOI: 10.3390/pharmaceutics15122702

Because of its efficient and robust gene transfer capability, messenger RNA (mRNA) has become a promising tool in various research fields. The lipid nanoparticle (LNP) is considered to be a fundamental technology for an mRNA delivery system and has been used extensively for the development of RNA vaccines against SARS-CoV-2. We recently developed ssPalm, an environmentally responsive lipid-like material, as a component of LNP for mRNA delivery. In this study, a self-degradable unit (phenyl ester) that confers high transfection activity and an immune stimulating unit (vitamin E scaffold) for high immune activation were combined to design a material, namely, ssPalmE-Phe-P4C2, for vaccine use. To design a simple and user-friendly form of an RNA vaccine based on this material, a freeze-drying-based preparation method for producing a ready-to-use-type LNP (LNP(RtoU)) was used to prepare the LNP . The optimization of the preparation method and the lipid composition of the LNP (RtoU) revealed that dioleoyl-sn-glycero phosphatidylethanolamine (DOPE) was a suitable helper lipid for achieving a high vaccination activity of the LNP (RtoU). Other findings indicated that to maintain particle properties and vaccination activity, a 40% cholesterol content was necessary. A single administration of the LNP (RtoU) that contained mRNA-encoding Ovalbumin (mOVA-LNP (RtoU)) demonstrated a significant suppression of tumor progression in a tumor-bearing mouse OVA-expressing cell line (E.G7-OVA). In summary, the LNP (RtoU) is an easy-to-handle drug delivery system (DDS) for delivering mRNA antigens in immunotherapy.