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

Author:

Anindita Jessica12,Tanaka Hiroki2,Oyama Ryotaro12,Hagiwara Shinya1,Shirane Daiki1,Taneichi Sakura3,Nakai Yuta3,Tange Kota3,Hatakeyama Hiroto1ORCID,Sakurai Yu2ORCID,Akita Hidetaka2ORCID

Affiliation:

1. Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-0856, Japan

2. Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan

3. Life Science Research Laboratory, NOF CORPORATION, 3-3 Chidori-cho, Kawasaki-ku, Kawasaki 210-0865, Japan

Abstract

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 LNPssPalmE-Phe. The optimization of the preparation method and the lipid composition of the LNPssPalmE-Phe(RtoU) revealed that dioleoyl-sn-glycero phosphatidylethanolamine (DOPE) was a suitable helper lipid for achieving a high vaccination activity of the LNPssPalmE-Phe(RtoU). Other findings indicated that to maintain particle properties and vaccination activity, a 40% cholesterol content was necessary. A single administration of the LNPssPalmE-Phe(RtoU) that contained mRNA-encoding Ovalbumin (mOVA-LNPssPalmE-Phe(RtoU)) demonstrated a significant suppression of tumor progression in a tumor-bearing mouse OVA-expressing cell line (E.G7-OVA). In summary, the LNPssPalmE-Phe(RtoU) is an easy-to-handle drug delivery system (DDS) for delivering mRNA antigens in immunotherapy.

Funder

JSPS KAKENHI

JST CREST

Basic Science and Platform Technology Program for Innovative Biological Medicine from the Japan Agency for Medical Research and Development

NOF CORPORATION

Publisher

MDPI AG

Subject

Pharmaceutical Science

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