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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
oleh: Jessica Anindita, Hiroki Tanaka, Ryotaro Oyama, Shinya Hagiwara, Daiki Shirane, Sakura Taneichi, Yuta Nakai, Kota Tange, Hiroto Hatakeyama, Yu Sakurai, Hidetaka Akita
| Format: | Article |
|---|---|
| Diterbitkan: | MDPI AG 2023-11-01 |
Deskripsi
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<sub>ssPalmE-Phe</sub>. The optimization of the preparation method and the lipid composition of the LNP<sub>ssPalmE-Phe</sub>(RtoU) revealed that dioleoyl-sn-glycero phosphatidylethanolamine (DOPE) was a suitable helper lipid for achieving a high vaccination activity of the LNP<sub>ssPalmE-Phe</sub>(RtoU). Other findings indicated that to maintain particle properties and vaccination activity, a 40% cholesterol content was necessary. A single administration of the LNP<sub>ssPalmE-Phe</sub>(RtoU) that contained mRNA-encoding Ovalbumin (mOVA-LNP<sub>ssPalmE-Phe</sub>(RtoU)) demonstrated a significant suppression of tumor progression in a tumor-bearing mouse OVA-expressing cell line (E.G7-OVA). In summary, the LNP<sub>ssPalmE-Phe</sub>(RtoU) is an easy-to-handle drug delivery system (DDS) for delivering mRNA antigens in immunotherapy.