Article
Immunology
Tanjila Hasan, Ryo Kawanishi, Hidetaka Akita, Yoshifumi Nishikawa
Summary: ssPalmE-LNP is an effective carrier for DNA vaccines against protozoan infections, leading to increased survival rates and antibody production in mice. Further immunological studies are needed to explore the mechanism of protective immunity induced by ssPalmE-LNPTgGRA15.
Article
Pharmacology & Pharmacy
Naoki Cho, Hiroshi Suemizu, Hidetaka Kamimura, Tomoyuki Ohe, Fumi Ito, Hidetaka Akita, Kaoru Kobayashi
Summary: This study used a humanized-liver mouse model to investigate the pharmacokinetic profiles of benzbromarone and the generation of reactive metabolites. The results showed that the metabolic profiles of benzbromarone in humanized-liver mice were similar to those in humans, and the detected reactive metabolites were associated with benzbromarone-induced hepatotoxicity.
DRUG METABOLISM AND PHARMACOKINETICS
(2022)
Article
Medicine, Research & Experimental
Keita Kitamura, Ayaka Okamoto, Hanae Morio, Ryuto Isogai, Ryo Ito, Yoshiyuki Yamaura, Saki Izumi, Takafumi Komori, Shingo Ito, Sumio Ohtsuki, Hidetaka Akita, Tomomi Furihata
Summary: This study characterizes the ability of the hiMCS-BBB models to evaluate receptor-mediated transcytosis (RMT)-mediated blood-brain barrier (BBB) penetration properties of middle/macromolecules. The results show that the hiMCS-BBB models have the potential to provide valuable tools for exploring and identifying middle/macromolecules with excellent BBB permeability levels.
MOLECULAR PHARMACEUTICS
(2022)
Article
Pharmacology & Pharmacy
Yu Sakurai, Himeka Watanabe, Kazuma Nishio, Kohei Hashimoto, Atsuki Harada, Masaki Gomi, Masayoshi Suzuki, Ryotaro Oyama, Takumi Handa, Risa Sato, Hina Takeuchi, Ryoga Taira, Kenta Tezuka, Kota Tange, Yuta Nakai, Hidetaka Akita, Yasuo Uchida
Summary: The blood-brain barrier plays a crucial role in drug transport, and studying proteins in endothelial cells is important for treating brain diseases. Researchers developed lipid nanoparticles (LNPs) to deliver mRNA into human brain capillary endothelial cells, resulting in high efficiency and low toxicity compared to a commercial transfection reagent.
Article
Chemistry, Multidisciplinary
Yu Sakurai, Nodoka Abe, Keito Yoshikawa, Ryotaro Oyama, Satoshi Ogasawara, Takeshi Murata, Yuta Nakai, Kota Tange, Hiroki Tanaka, Hidetaka Akita
Summary: This study developed a method for selective delivery of siRNA to LECs using LNPs. The method of modifying LNPs used in the study shows promise for expanding the delivery of nucleic acids in the future.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Chemistry, Multidisciplinary
Hiroki Tanaka, Shinya Hagiwara, Daiki Shirane, Takuma Yamakawa, Yuka Sato, Chika Matsumoto, Kota Ishizaki, Miho Hishinuma, Katsuyuki Chida, Kasumi Sasaki, Etsuo Yonemochi, Keisuke Ueda, Kenjirou Higashi, Kunikazu Moribe, Takashi Tadokoro, Katsumi Maenaka, Sakura Taneichi, Yuta Nakai, Kota Tange, Yu Sakurai, Hidetaka Akita
Summary: There is a growing demand by researchers to test whether their own biological findings might be applicable for use in mRNA-based therapeutics, but the equipment and know-how required for manufacturing such nanoparticles is often inaccessible. A simple method for preparing mRNA-LNPs is prerequisite to encourage more innovation in mRNA therapeutics. This study reports on a method for encapsulating IVT-mRNA into LNPs by rehydrating a Ready-to-Use empty freeze-dried LNP formulation with IVT-mRNA solution followed by heating, and the resulting mRNA-LNPs had a similar structure compared to the mRNA-LNPs prepared by conventional microfluidic mixing. In vivo genome editing using these mRNA-LNPs was achieved.
Article
Chemistry, Multidisciplinary
Yu Sakurai, Keito Yoshikawa, Kenta Arai, Akira Kazaoka, Shigeki Aoki, Kousei Ito, Yuta Nakai, Kota Tange, Tomomi Furihata, Hiroki Tanaka, Hidetaka Akita
Summary: This study targets lymphatic endothelial cells (LEC) using ionizable lipid-formulated nanoparticles (LNPs) complexed with Apolipoprotein E (ApoE). The LNPs are taken up by LECs in an ApoE-dependent manner, as shown in in vitro studies. Modifying the surface of the LNPs with a high density of PEG-conjugated lipids with short acyl chains enables effective targeting of LECs after subcutaneous administration. This approach significantly inhibits the expression of the LEC marker VEGFR3.
JOURNAL OF CONTROLLED RELEASE
(2023)
Article
Chemistry, Multidisciplinary
Mizuki Doi, Hiroki Tanaka, Takara Ohoto, Naoya Miura, Yu Sakurai, Hiroto Hatakeyama, Hidetaka Akita
Summary: The reactivation of anticancer immunity using immune checkpoint inhibitors (ICIs) is a crucial aspect in cancer immunotherapy. However, the low objective response rate (<40%) of ICIs remains a major challenge. This study demonstrates that myeloid-derived suppressor cells (MDSCs) can be depleted by delivering synthetic glucocorticoid dexamethasone to phagocytic cells in the spleen using lipid nanoparticles. Additionally, the nanoparticulated dexamethasone exhibits a synergistic anticancer effect with ICIs.
Article
Engineering, Biomedical
Masaki Gomi, Yu Sakurai, Minami Sato, Hiroki Tanaka, Yumi Miyatake, Koichi Fujiwara, Mizuki Watanabe, Satoshi Shuto, Yuta Nakai, Kota Tange, Hiroto Hatakeyama, Hidetaka Akita
Summary: This study reports the development of a new lipid nanoparticle (LNP) that efficiently delivers messenger RNA (mRNA) to secondary lymphoid tissues. A microfluidic technique was used to incorporate alcohol-soluble phosphatidylserine (PS) derivatives, designed to target immune cells, into LNPs with high scalability and reproducibility. The resulting PS-loaded LNP delivered mRNA to the spleen more efficiently than a control LNP. Sub-organ analysis revealed extensive uptake of the PS-loaded LNP by tissue-resident macrophages in the red pulp and marginal zone of the spleen. Therefore, the PS-loaded LNP described in this study holds promise for clinical applications involving mRNA delivery to the spleen.
ADVANCED HEALTHCARE MATERIALS
(2023)
Article
Biochemistry & Molecular Biology
Sumiyo Morita, Takuro Horii, Mika Kimura, Ryosuke Kobayashi, Hiroki Tanaka, Hidetaka Akita, Izuho Hatada
Summary: Knockout mice are important tools for studying the normal function of genes. Liver-specific conditional knockout mice can be generated using lipid nanoparticles, which offers a more convenient method compared to traditional approaches.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Daiki Shirane, Hiroki Tanaka, Yu Sakurai, Sakura Taneichi, Yuta Nakai, Kota Tange, Itsuko Ishii, Hidetaka Akita
Summary: The lipid nanoparticle (LNP) is a promising nanotechnology for delivering RNA molecules, including siRNA and mRNA. LNPs encoding the antigen protein of SARS-CoV-2 have been approved as mRNA vaccines against the disease. LNP formulations are generally metastable, and their properties can shift towards a more stable state during long-term storage. To enable easier storage, a one-pot method was used to prepare freeze-dried formulations of mRNA-LNPs that can be stored at 4°C for at least 4 months.
Article
Pharmacology & Pharmacy
Xuan Du, Erica Yada, Yuki Terai, Takuya Takahashi, Hideyuki Nakanishi, Hiroki Tanaka, Hidetaka Akita, Keiji Itaka
Summary: This study compared the performance of nanomicelles and LNPs in mRNA delivery. The nanomicelles showed relatively sustained protein production and reduced inflammation, making them suitable for therapeutic purposes, while LNPs exhibited rapid mRNA expression and a potent immune response, making them suitable for vaccine purposes. These results provide support for further optimization of mRNA delivery systems tailored for specific purposes.
Article
Chemistry, Medicinal
Masaki Gomi, Yuka Nakayama, Yu Sakurai, Ryotaro Oyama, Koki Iwasaki, Mizuki Doi, Yi Liu, Mizuho Hori, Himeka Watanabe, Kohei Hashimoto, Hiroki Tanaka, Kota Tange, Yuta Nakai, Hidetaka Akita
Summary: This study investigates the delivery of mRNA encoding autoantigens to the spleen using lipid nanoparticles (LNPs) containing phosphatidylserine (PS). The expressed MOG35-55 antigens induce immune tolerance and could potentially be used as a treatment for experimental autoimmune encephalitis (EAE).
Article
Pharmacology & Pharmacy
Yuki Noguchi, Kazuhisa Ozeki, Hidetaka Akita
Summary: This study proposes a new cell-based assay using human liver non-parenchymal cells (NPC) for evaluating the binding and internalization of biologics. By staining NPC with CD31 and CD45 and analyzing them through flow cytometry, the LSEC population was identified. The findings indicate that using fresh human liver NPC for cell-based assays can effectively evaluate the binding and internalization of biologics, as well as determine pharmacokinetic parameters.
BIOLOGICAL & PHARMACEUTICAL BULLETIN
(2022)
Review
Chemistry, Organic
Hiroki Tanaka, Hidetaka Akita
Summary: Specialized medicine is now expanding from low-molecular drugs to recombinant proteins, antibodies, and nucleic acids. Among them, RNA therapy is growing worldwide as an alternative gene complement approach. The use of short nucleic acids such as siRNA and miRNA to regulate disease-related genes shows promising results in the field of medicine.
JOURNAL OF SYNTHETIC ORGANIC CHEMISTRY JAPAN
(2022)