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Masaharu Somiya

Section

Institute of Multidisciplinary Research for Advanced Materials

Job title

Associate Professor

Degree

Doctor of Agriculture (Nagoya University)

researchmap

https://researchmap.jp/masaharusomiya

J-GLOBAL ID

201601001937081766

Researcher ID

J-9042-2018

Research History 9

2026/04 - Present

Tohoku University　Institute of Multidisciplinary Research for Advanced Materials, Division of Organic- and Bio-materials Research　Associate Professor
2024/06 - 2026/03

Osaka University　SANKEN　Associate Professor
2017/06 - 2024/05

Osaka University　The Institute of Scientific and Industrial Research　Assistant Professor
2022/02 - 2024/02

Japan Society for the Promotion of Science　Overseas Research Fellowship
2022/02 - 2024/02

University of Washington　Institute for Protein Design　Visiting Scholar (Neil King lab)
2017/04 - 2017/05

National Cancer Center Research Institute　Division of Molecular and Cellular Medicine　Visiting researcher
2017/04 - 2017/05

JSPS　JSPS Research Fellow SPD
2016/04 - 2017/03

National Cancer Center　Research Institute, Department of Molecular and Cellular Medicine　Postdoctoral researcher
2013/04 - 2016/03

JSPS　JSPS Research Fellowships for Young Scientists DC1

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Education 4

Nagoya University　Graduate School of Bioagricultural Sciences

2011/04 - 2016/03
Massachusetts Institute of Technology　Department of Chemical Engineering

2014/01 - 2014/03
Kitakyushu National College of Technology　Advanced Engineering School

2009/04 - 2011/03
Kitakyushu National College of Technology　Department of Materials Science & Chemical Engineering

2004/04 - 2009/03

Committee Memberships 5

日本生物工学会生物工学若手研究者の集い（生物工学若手会）　会長

2025/09 - Present
日本生物工学会次世代アニマルセルインダストリー研究部会　運営委員（HP＆メーリングリスト担当）

2018/04 - 2026/03
日本生物工学会生物工学若手研究者の集い（生物工学若手会）　副会長

2023/09 - 2025/09
日本生物工学会生物工学若手研究者の集い（生物工学若手会）　役員（会計）

2021/10 - 2023/09
日本生物工学会生物工学若手研究者の集い（生物工学若手会）　役員（ホームページ・フォーラム担当）

2019/09 - 2021/10

Professional Memberships 6

日本細胞生物学会
日本生物物理学会
Japanese Society for Extracellular Vesicles
International Society for Extracellular Vesicles
The Society for Biotechnology, Japan
THE JAPAN SOCIETY OF DRUG DELIVERY SYSTEM

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Research Interests 9

Protein editing
Protein design
細胞外小胞
合成生物学
liposome
Nucleic acid medicines
Hepatitis B virus
Exosomes
Drug delivery systems

Research Areas 4

Nanotechnology/Materials / Molecular biochemistry /
Life sciences / Structural biochemistry /
Nanotechnology/Materials / Nanobioscience /
Life sciences / Biomaterials /

Awards 11

令和７年度大阪大学賞（若手教員部門）

2025/11　大阪大学　計算機で設計した人工タンパク質を利用した薬物送達技術の研究
Scholarship for ISEV2021

2021/05　International Society for Extracellular Vesicles　Reporter gene assay for membrane fusion and cytoplasmic cargo delivery of extracellular vesicles
第7回日本細胞外小胞学会学術集会奨励賞

2020/10　日本細胞外小胞学会JSEV　細胞外小胞のレシピエント細胞内での内包物放出を定量化するアッセイ系の開発
Outstanding Team Presentation at Interstellar Initiative 2018 Workshop

2018/06　AMED and NYAS　Discovery of Novel Therapeutics in Kidney Cancer
Poster Presentation Award

2017/12　公益財団法人川崎市産業振興財団　Bioavailability of bovine milk-derived exosome for drug delivery application
Oral Presentation Award

2017/09　日本RNAi研究会・日本細胞外小胞学会　牛乳由来細胞外小胞のドラッグデリバリーシステムへの応用
IGER Annual meeting 2015 Poster Award

2016/01　名古屋大学グリーン自然科学国際教育研究プログラム
IGER Annual Meeting 2014 Annual Research Award

2015/01　名古屋大学グリーン自然科学国際教育研究プログラム
2014年度日本生物工学会中部支部長賞

2014/08　日本生物工学会中部支部　バイオナノカプセル-リポソーム複合体によるヒト肝臓細胞特異的な細胞質への物質送達機構の解明
2013年度日本生物工学会生物工学学生優秀賞 (飛翔賞）

2013/09　日本生物工学会　効率的な薬物・遺伝子送達に向けたバイオナノカプセル-リポソーム複合体の細胞内動態の解析と制御技術開発
2013年度 Young Researcher’s Award（研究奨励賞）

2013/07　日本生物工学会セルプロセッシング計測評価研究部会　バイオナノカプセル-リポソーム複合体の細胞内侵入機構に基づいたナノキャリア開発

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Papers 52

Computational design of membrane fusion proteins. International-journal

Masaharu Somiya, Sydney Funk, Dane Zambrano, Takumi Yanase, Noriyuki Hamaoka, Alex Kang, Banumathi Sankaran, Asim K Bera, Neil P King

bioRxiv : the preprint server for biology　2026/05/07

DOI： 10.64898/2026.05.04.722779 　

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The fusion of two distinct biological membranes is an evolutionarily conserved process essential to cellular organization and physiology. Membrane fusion is driven by the refolding of fusogenic proteins into low-energy postfusion states that overcome the energetic barrier to bilayer merger. Here we report a computational method for the design of synthetic fusogens inspired by the architecture of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex. Using machine learning-guided protein design to extensively remodel backbone geometry and sequence, we generated heterodimeric SNARE-like assemblies that efficiently catalyze cell-cell membrane fusion. These minimal two-component fusogens exhibit substantially higher fusion activity than native multisubunit SNARE complexes. Structural and functional analyses identify the key determinants required for fusogenic activity and reveal a modularity that enables control of fusion through chemically induced heterodimerization. In addition to cell-cell fusion, the synthetic fusogens drive fusion between endoplasmic reticulum and mitochondrial membranes from human cells, demonstrating their potential as tools for programmable manipulation of intracellular membranes. Together, these results establish a general framework for the rational design of synthetic fusogens and expand the toolkit for engineering membrane dynamics in living systems.
Programmable protein editing by split intein-mediated recombination

Masaharu Somiya, Takumi Yanase

bioRxiv　2026/01

DOI： 10.64898/2026.01.22.700961 　
Computational design of non-porous pH-responsive antibody nanoparticles. International-journal Peer-reviewed

Erin C Yang, Robby Divine, Marcos C Miranda, Andrew J Borst, Will Sheffler, Jason Z Zhang, Justin Decarreau, Amijai Saragovi, Mohamad Abedi, Nicolas Goldbach, Maggie Ahlrichs, Craig Dobbins, Alexis Hand, Suna Cheng, Mila Lamb, Paul M Levine, Sidney Chan, Rebecca Skotheim, Jorge Fallas, George Ueda, Joshua Lubner, Masaharu Somiya, Alena Khmelinskaia, Neil P King, David Baker

Nature structural & molecular biology　2024/05/09

DOI： 10.1038/s41594-024-01288-5 　

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Programming protein nanomaterials to respond to changes in environmental conditions is a current challenge for protein design and is important for targeted delivery of biologics. Here we describe the design of octahedral non-porous nanoparticles with a targeting antibody on the two-fold symmetry axis, a designed trimer programmed to disassemble below a tunable pH transition point on the three-fold axis, and a designed tetramer on the four-fold symmetry axis. Designed non-covalent interfaces guide cooperative nanoparticle assembly from independently purified components, and a cryo-EM density map closely matches the computational design model. The designed nanoparticles can package protein and nucleic acid payloads, are endocytosed following antibody-mediated targeting of cell surface receptors, and undergo tunable pH-dependent disassembly at pH values ranging between 5.9 and 6.7. The ability to incorporate almost any antibody into a non-porous pH-dependent nanoparticle opens up new routes to antibody-directed targeted delivery.
Engineering of Extracellular Vesicles for Small Molecule-Regulated Cargo Loading and Cytoplasmic Delivery of Bioactive Proteins. International-journal Peer-reviewed

Masaharu Somiya, Shun'ichi Kuroda

Molecular pharmaceutics　2022/05/20

DOI： 10.1021/acs.molpharmaceut.2c00192 　

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Cytoplasmic delivery of functional proteins into target cells remains challenging for many biological agents to exert their therapeutic effects. Extracellular vesicles (EVs) are expected to be a promising platform for protein delivery; however, efficient loading of proteins of interest (POIs) into EVs remains elusive. In this study, we utilized small compound-induced heterodimerization between FK506 binding protein (FKBP) and FKBP12-rapamycin-binding (FRB) domain to sort bioactive proteins into EVs using the FRB-FKBP system. When CD81, a typical EV marker protein, and POI were fused with FKBP and FRB, respectively, rapamycin induced the binding of these proteins through the FKBP-FRB interaction and recruited the POIs into EVs. The released EVs, displaying the virus-derived membrane fusion protein, delivered the POI cargo into recipient cells and their functionality in the recipient cells was confirmed. Furthermore, we demonstrated that CD81 could be replaced with other EV-enriched proteins, such as CD63 or HIV Gag. Thus, the FRB-FKBP system enables the delivery of functional proteins and paves the way for EV-based protein delivery platforms.
Reporter gene assay for membrane fusion of extracellular vesicles Peer-reviewed

Masaharu Somiya, Shun{\textquotesingle}ichi Kuroda

Journal of Extracellular Vesicles　10　(13)　2021/11/22
Publisher: Wiley
DOI： 10.1002/jev2.12171 　

ISSN： 2001-3078
Real-Time Luminescence Assay for Cytoplasmic Cargo Delivery of Extracellular Vesicles Peer-reviewed

Masaharu Somiya, Shun’ichi Kuroda

Analytical Chemistry　2021/03
Publisher: American Chemical Society ({ACS})
DOI： 10.1021/acs.analchem.1c00339 　

ISSN： 0003-2700

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<jats:title>Abstract</jats:title><jats:p>Extracellular vesicles (EVs) have been considered to deliver biological cargos betweencells and mediate intercellular communication. However, the mechanisms that underlie the biological process of EV uptake and cytoplasmic cargo release in recipient cells are largely unknown. Quantitative and real-time assays for assessment of the cargo delivery efficiency inside recipient cells have not been feasible. In this study, we developed an EV cargo delivery (EVCD) assay using a split luciferase called the NanoBiT system. Recipient cells expressing LgBiT, a large subunit of luciferase, emit luminescence when the EV cargo proteins fused with a small luminescence tag (HiBiT tag) that can complement LgBiT are delivered to the cytoplasm of recipient cells. Using the EVCD assay, the cargo delivery efficiency of EVs could be quantitatively measured in real time. This assay was highly sensitive in detecting a single event of cargo delivery per cell. We found that modification of EVs with a virus-derived fusogenic protein significantly enhanced the cytoplasmic cargo delivery; however, in the absence of a fusogenic protein, the cargo delivery efficiency of EVs was below the threshold of the assay. The EVCD assay could assess the effect of entry inhibitors on EV cargo delivery. Furthermore, using a luminescence microscope, the cytoplasmic cargo delivery of EVs was directly visualized in living cells. This assay could reveal the biological mechanism of the cargo delivery processes of EVs.</jats:p>
Biocompatibility of highly purified bovine milk-derived extracellular vesicles International-journal Peer-reviewed

Somiya, M., Yoshioka, Y., Ochiya, T.

Journal of Extracellular Vesicles　7　(1)　1440132-1440132　2018
Publisher: Taylor and Francis Ltd.
DOI： 10.1080/20013078.2018.1440132 　

ISSN： 2001-3078
タンパク質デザインの薬物送達システムへの応用 Invited

曽宮正晴

生体の科学　76　(2)　126-130　2025/04

DOI： 10.11477/mf.037095310760020126 　
Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches Peer-reviewed

Joshua A. Welsh, Deborah C. I. Goberdhan, Lorraine O'Driscoll, Edit I. Buzas, Cherie Blenkiron, Benedetta Bussolati, Houjian Cai, Dolores Di Vizio, Tom A. P. Driedonks, Uta Erdbrügger, Juan M. Falcon‐Perez, Qing‐Ling Fu, Andrew F. Hill, Metka Lenassi, Sai Kiang Lim, Mỹ G. Mahoney, Sujata Mohanty, Andreas Möller, Rienk Nieuwland, Takahiro Ochiya, Susmita Sahoo, Ana C. Torrecilhas, Lei Zheng, Andries Zijlstra, Sarah Abuelreich, Reem Bagabas, Paolo Bergese, Esther M. Bridges, Marco Brucale, Dylan Burger, Randy P. Carney, Emanuele Cocucci, Rossella Crescitelli, Edveena Hanser, Adrian L. Harris, Norman J. Haughey, An Hendrix, Alexander R. Ivanov, Tijana Jovanovic‐Talisman, Nicole A. Kruh‐Garcia, Vroniqa Ku'ulei‐Lyn Faustino, Diego Kyburz, Cecilia Lässer, Kathleen M. Lennon, Jan Lötvall, Adam L. Maddox, Elena S. Martens‐Uzunova, Rachel R. Mizenko, Lauren A. Newman, Andrea Ridolfi, Eva Rohde, Tatu Rojalin, Andrew Rowland, Andras Saftics, Ursula S. Sandau, Julie A. Saugstad, Faezeh Shekari, Simon Swift, Dmitry Ter‐Ovanesyan, Juan P. Tosar, Zivile Useckaite, Francesco Valle, Zoltan Varga, Edwin van der Pol, Martijn J. C. van Herwijnen, Marca H. M. Wauben, Ann M. Wehman, Sarah Williams, Andrea Zendrini, Alan J. Zimmerman, Clotilde Théry, Kenneth W. Witwer

Journal of Extracellular Vesicles　13　(2)　2024/02/07
Publisher: Wiley
DOI： 10.1002/jev2.12404 　

ISSN： 2001-3078

eISSN： 2001-3078

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Abstract Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year‐on‐year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non‐vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its ‘Minimal Information for Studies of Extracellular Vesicles’, which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly.
Computational design of non-porous, pH-responsive antibody nanoparticles

Erin C. Yang, Robby Divine, Marcos C. Miranda, Andrew J. Borst, Will Sheffler, Jason Z Zhang, Justin Decarreau, Amijai Saragovi, Mohamad Abedi, Nicolas Goldbach, Maggie Ahlrichs, Craig Dobbins, Alexis Hand, Suna Cheng, Mila Lamb, Paul M. Levine, Sidney Chan, Rebecca Skotheim, Jorge Fallas, George Ueda, Joshua Lubner, Masaharu Somiya, Alena Khmelinskaia, Neil P. King, David Baker

2023/04/18
Publisher: Cold Spring Harbor Laboratory
DOI： 10.1101/2023.04.17.537263 　

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Abstract Programming protein nanomaterials to respond to changes in environmental conditions is a current challenge for protein design and important for targeted delivery of biologics. We describe the design of octahedral non-porous nanoparticles with the three symmetry axes (four-fold, three-fold, and two-fold) occupied by three distinct protein homooligomers: ade novodesigned tetramer, an antibody of interest, and a designed trimer programmed to disassemble below a tunable pH transition point. The nanoparticles assemble cooperatively from independently purified components, and a cryo-EM density map reveals that the structure is very close to the computational design model. The designed nanoparticles can package a variety of molecular payloads, are endocytosed following antibody-mediated targeting of cell surface receptors, and undergo tunable pH-dependent disassembly at pH values ranging between to 5.9-6.7. To our knowledge, these are the first designed nanoparticles with more than two structural components and with finely tunable environmental sensitivity, and they provide new routes to antibody-directed targeted delivery.
Progress of Endogenous and Exogenous Nanoparticles for Cancer Therapy and Diagnostics Peer-reviewed

Hideaki Fujita, Seiichi Ohta, Noriko Nakamura, Masaharu Somiya, Masanobu Horie

Genes　14　(2)　259-259　2023/01/19
Publisher: MDPI AG
DOI： 10.3390/genes14020259 　

eISSN： 2073-4425

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The focus of this brief review is to describe the application of nanoparticles, including endogenous nanoparticles (e.g., extracellular vesicles, EVs, and virus capsids) and exogenous nanoparticles (e.g., organic and inorganic materials) in cancer therapy and diagnostics. In this review, we mainly focused on EVs, where a recent study demonstrated that EVs secreted from cancer cells are associated with malignant alterations in cancer. EVs are expected to be used for cancer diagnostics by analyzing their informative cargo. Exogenous nanoparticles are also used in cancer diagnostics as imaging probes because they can be easily functionalized. Nanoparticles are promising targets for drug delivery system (DDS) development and have recently been actively studied. In this review, we introduce nanoparticles as a powerful tool in the field of cancer therapy and diagnostics and discuss issues and future prospects.
Recent advances in animal cell technologies for industrial and medical applications. Peer-reviewed

Masanobu Horie, Noriko Yamano-Adachi, Yoshinori Kawabe, Hidenori Kaneoka, Hideaki Fujita, Eiji Nagamori, Ryosuke Iwai, Yasushi Sato, Kei Kanie, Seiichi Ohta, Masaharu Somiya, Kosuke Ino

Journal of bioscience and bioengineering　133　(6)　509-514　2022/06

DOI： 10.1016/j.jbiosc.2022.03.005 　

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The industrial use of living organisms for bioproduction of valued substances has been accomplished mostly using microorganisms. To produce high-value bioproducts such as antibodies that require glycosylation modification for better performance, animal cells have been recently gaining attention in bioengineering because microorganisms are unsuitable for producing such substances. Furthermore, animal cells are now classified as products because a large number of cells are required for use in regenerative medicine. In this article, we review animal cell technologies and the use of animal cells, focusing on useable cell generation and large-scale production of animal cells. We review recent advance in mammalian cell line development because this is the first step in the production of recombinant proteins, and it largely affects the efficacy of the production. We next review genetic engineering technology focusing on CRISPR-Cas system as well as surrounding technologies as these methods have been gaining increasing attention in areas that use animal cells. We further review technologies relating to bioreactors used in the context of animal cells because they are essential for the mass production of target products. We also review tissue engineering technology because tissue engineering is one of the main exits for mass-produced cells; in combination with genetic engineering technology, it can prove to be a promising treatment for patients with genetic diseases after the establishment of induced pluripotent stem cell technology. The technologies highlighted in this review cover brief outline of the recent animal cell technologies related to industrial and medical applications.
Comment on "Cutting Edge: Circulating Exosomes with COVID Spike Protein Are Induced by BNT162b2 (Pfizer-BioNTech) Vaccination prior to Development of Antibodies: A Novel Mechanism for Immune Activation by mRNA Vaccines". International-journal Peer-reviewed

Masaharu Somiya

Journal of immunology (Baltimore, Md. : 1950)　208　(8)　1833-1833　2022/04/15

DOI： 10.4049/jimmunol.2101082 　
Verification of extracellular vesicle-mediated functional mRNA delivery via RNA editing

Somiya, Masaharu, Kuroda, Shun{\textquoteright}ichi

bioRxiv　2022/01/26
Publisher: Cold Spring Harbor Laboratory
DOI： 10.1101/2022.01.25.477620 　

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The secretion and delivery of mRNA by extracellular vesicles (EVs) may contribute to intercellular communications. Several reporter assays have been developed to quantify EV-mediated functional delivery of mRNA into recipient cells. However, mRNA delivery efficiency can often be overestimated by experimental artifacts, resulting in "pseudo-delivery" of reporter proteins rather than mRNA. In this study, we revealed that substantial amounts of reporter proteins expressed in donor cells are secreted into the medium and interfere with the reporter assay. To eliminate this pseudo-delivery, we established a functional RNA delivery assay that employs an RNA editing tool, enabling the verification of bona fide delivery of mRNA into recipient cells. The donor cells expressed a reporter gene containing a stop codon in a non-functional open reading frame. After EV-mediated delivery of reporter mRNAs to the recipient cells, guide RNAs and RNA editing enzymes (dCas13b-hADAR2 fusion proteins) correct the RNA sequence and induce the expression of functional reporter proteins in the recipient cells. Using this system, we showed that EVs containing alphavirus-derived replicon successfully delivered functional RNA and expressed the reporter proteins. The RNA delivery assay using RNA editing enables the precise analysis of EV-mediated mRNA delivery.
Engineering of extracellular vesicles for small molecule-regulated cargo loading and cytoplasmic delivery of bioactive proteins

Masaharu Somiya, Shun{\textquotesingle}ichi Kuroda

bioRxiv　2021/11/05
Publisher: Cold Spring Harbor Laboratory
DOI： 10.1101/2021.11.04.466099 　

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<jats:p>Cytoplasmic delivery of functional proteins into target cells remains challenging for many biological agents to exert their therapeutic effects. Extracellular vesicles (EVs) are expected to be a promising platform for protein delivery; however, efficient loading of proteins of interest (POIs) into EVs remains elusive. In this study, we utilized small compound-induced heterodimerization between FK506 binding protein (FKBP) and FKBP12-rapamycin-binding (FRB) domain, to sort bioactive proteins into EVs using the FRB-FKBP system. When CD81, a typical EV marker protein, and POI were fused with FKBP and FRB, respectively, rapamycin induced the binding of these proteins through FKBP-FRB interaction and recruited the POIs into EVs. The released EVs, displaying virus-derived membrane fusion protein, delivered the POI cargo into recipient cells and their functionality in the recipient cells was confirmed. Furthermore, we demonstrated that CD81 could be replaced with other EV-enriched proteins, such as CD63 or HIV Gag. Thus, the FRB-FKBP system enables the delivery of functional proteins and paves the way for EV-based protein delivery platforms.</jats:p>
HBV Pre-S1-Derived Myristoylated Peptide (Myr47): Identification of the Inhibitory Activity on the Cellular Uptake of Lipid Nanoparticles Peer-reviewed

Masaya Nanahara, Ya-Ting Chang, Masaharu Somiya, Shun'ichi Kuroda

Viruses　13　(5)　929-929　2021/05/17
Publisher: {MDPI} {AG}
DOI： 10.3390/v13050929 　

ISSN： 1999-4915

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<jats:p>The Myr47 lipopeptide, consisting of hepatitis B virus (HBV) pre-S1 domain (myristoylated 2–48 peptide), is an effective commercialized anti-HBV drug that prevents the interaction of HBV with sodium taurocholate cotransporting polypeptide (NTCP) on human hepatocytes, an activity which requires both N-myristoylation residue and specific amino acid sequences. We recently reported that Myr47 reduces the cellular uptake of HBV surface antigen (HBsAg, subviral particle of HBV) in the absence of NTCP expression. In this study, we analyzed how Myr47 reduces the cellular uptake of lipid nanoparticles (including liposomes (LPs) and HBsAg) without NTCP expression. By using Myr47 mutants lacking the HBV infection inhibitory activity, they could reduce the cellular uptake of LPs in an N-myristoylation-dependent manner and an amino acid sequence-independent manner, not only in human liver-derived cells but also in human non-liver-derived cells. Moreover, Myr47 and its mutants could reduce the interaction of LPs with apolipoprotein E3 (ApoE3) in an N-myristoylation-dependent manner regardless of their amino acid sequences. From these results, lipopeptides are generally anchored by inserting their myristoyl residue into the lipid bilayer and can inhibit the interaction of LPs/HBsAg with apolipoprotein, thereby reducing the cellular uptake of LPs/HBsAg. Similarly, Myr47 would interact with HBV, inhibiting the uptake of HBV into human hepatic cells, while the inhibitory effect of Myr47 may be secondary to its ability to protect against HBV infection.</jats:p>
Sex differences in the incidence of anaphylaxis to LNP-mRNA COVID-19 vaccines International-journal

Masaharu Somiya, Sohtaro Mine, Kosuke Yasukawa, Saki Ikeda

Vaccine　39　(25)　3313-3314　2021/05
Publisher: Elsevier {BV}
DOI： 10.1016/j.vaccine.2021.04.066 　

ISSN： 0264-410X
Polymerized Albumin Receptor of Hepatitis B Virus for Evading the Reticuloendothelial System Peer-reviewed

Kurumi Takagi, Masaharu Somiya, Joohee Jung, Masumi Iijima, Shun'ichi Kuroda

Pharmaceuticals　2021/04

DOI： 10.3390/ph14050408 　
Cytoplasmic delivery of small interfering RNA by photoresponsive non-cationic liposomes Peer-reviewed

Masaharu Somiya, Kanako Sakaeda, Yuta Ishii, Shun’ichi Kuroda

Journal of Drug Delivery Science and Technology　102488-102488　2021/03
Publisher: Elsevier {BV}
DOI： 10.1016/j.jddst.2021.102488 　

ISSN： 1773-2247
Reporter gene assay for membrane fusion of extracellular vesicles

Masaharu Somiya, Shun'ichi Kuroda

bioRxiv　2021/02/17
Publisher: Cold Spring Harbor Laboratory
DOI： 10.1101/2021.02.16.431359 　

ISSN： 2001-3078

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<sec><title>Abstract</title>Extracellular vesicles (EVs) secreted by living cells are expected to deliver biological cargo molecules, including RNA and proteins, to the cytoplasm of recipient cells. There is an increasing need to understand the mechanism of intercellular cargo delivery by EVs. However, the lack of a feasible bioassay has hampered our understanding of the biological processes of EV uptake, membrane fusion, and cargo delivery to recipient cells. Here, we describe a reporter gene assay that can measure the membrane fusion efficiency of EVs during cargo delivery to recipient cells. When EVs containing tetracycline transactivator (tTA)-fused tetraspanins are internalized by recipient cells and fuse with cell membranes, the tTA domain is exposed to the cytoplasm and cleaved by protease to induce tetracycline responsive element (TRE)-mediated reporter gene expression in recipient cells. This assay (designated as <bold>E</bold>V-mediated <bold>t</bold>etraspanin-<bold>t</bold>TA <bold>d</bold>elivery assay, ETTD assay), enabled us to assess the cytoplasmic cargo delivery efficiency of EVs in recipient cells. With the help of a vesicular stomatitis virus-derived membrane fusion protein, the ETTD assay could detect significant enhancement of cargo delivery efficiency of EVs. Furthermore, the ETTD assay could evaluate the effect of potential cargo delivery enhancers/inhibitors. Thus, the ETTD assay may contribute to a better understanding of the underlying mechanism of the cytoplasmic cargo delivery by EVs. </sec>
Enhancing antibody-dependent cellular phagocytosis by Re-education of tumor-associated macrophages with resiquimod-encapsulated liposomes International-journal

Hao Li, Masaharu Somiya, Shun'ichi Kuroda

Biomaterials　268　120601-120601　2021/01
Publisher: Elsevier {BV}
DOI： 10.1016/j.biomaterials.2020.120601 　

ISSN： 0142-9612

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Tumor-associated macrophages (TAMs) exist in nearly all tumors, and form a major part of the tumor microenvironment. TAMs are divided into two groups: tumor-suppressing M1 type and tumor-promoting M2 type. Most TAMs are educated by the tumor cells to become M2 type, which support tumor growth and make immunotherapy ineffective. Antibody-dependent cellular phagocytosis (ADCP) is an important mechanism for antibody cancer therapy, and this mechanism is dependent on TAMs. In this study, we found that the M1 type macrophages elicit a more efficient ADCP response than the M2 type, which was confirmed by three tumor cell lines, Raji, A431, and SKBR3, along with their corresponding therapeutic antibody Rituximab, anti-EGFR mouse monoclonal antibody (clone 528), and Trastuzumab, respectively. Resiquimod (R848), an immune system activating agent, has been shown to stimulate the M1 type macrophages, and re-educate the TAMs from M2 type to M1 type. By treating TAMs with R848, the ADCP response increased significantly in vitro and in in vivo mouse xenograft models. R848 encapsulated liposomes (R848-LPs) not only accumulated efficiently in the tumor tissues, but also distributed in the TAMs. Synergizing the R848-LPs with the anti-EGFR mouse monoclonal antibody (clone 528) significantly inhibited WiDr-tumor growth in vivo. Our study also revealed that the TAM-targeted delivery of R848 is able to re-educate the TAMs to M1 type, enhance the ADCP effect of the antibodies, and hence, enhance the anti-tumor effect of the therapeutic antibodies.
A regulatory role of scavenger receptor class B type 1 in endocytosis and lipid droplet formation induced by liposomes containing phosphatidylethanolamine in HEK293T cells International-journal Peer-reviewed

Kazuyo Fujita, Narumi Koide, Masaharu Somiya, Shun{\textquotesingle}ichi Kuroda, Shuji Hinuma

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research　1868　(1)　118859-118859　2021/01
Publisher: Elsevier {BV}
DOI： 10.1016/j.bbamcr.2020.118859 　

ISSN： 0167-4889

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We have recently reported that phosphatidylethanolamine (PE)-containing liposomes are endocytosed and then induce lipid droplets (LDs) in HEK293T cells. In this study, we elucidated a mechanism responsible for endocytosis of PE-containing liposomes and induction of LDs. By using fluorescence-labeled liposomes and flow cytometry, we found that PE-containing liposomes were very efficiently internalized in HEK293T cells. However, Block lipid transporter-1 (BLT-1) only marginally suppressed the uptake of these liposomes, indicating that entire liposomes were mostly taken up in these cells. They were therefore inferred to express abundant PE receptors responsible for endocytosis of PE-containing liposomes. We examined the expression of 52 candidate genes through transcriptomic analyses and eventually narrowed it down to four candidate genes, which were abundantly expressed in HEK293T cells. Among siRNAs targeting these candidates, scavenger receptor class B type 1 (SR-B1) siRNA showed the most profound reduction in PE liposomal uptake. Conversely, the expression of SR-B1 by transfection of an expression plasmid enhanced the uptake of PE-containing liposomes. After the internalization of PE-containing liposomes, they were colocalized with endosomes/lysosomes and SR-B1, which indicates that these liposomes are taken up in HEK293T cells at least partially through the endosomal/lysosomal pathway. A specific anti-SR-B1-antibody blocked the uptake of PE-containing liposomes in HEK293T cells while LD formation in these cells induced by PE-containing liposomes was suppressed by treatment with SR-B1 siRNA. These results demonstrate that SR-B1 functions as a receptor for the endocytosis of PE-containing liposomes and regulates the formation of LDs induced by PE-containing liposomes in HEK293T cells.
Real-time luminescence assay for cytoplasmic cargo delivery of extracellular vesicles

Masaharu Somiya, Shun'ichi Kuroda

bioRxiv　2020/10/16
Publisher: Cold Spring Harbor Laboratory
DOI： 10.1101/2020.10.16.341974 　

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<jats:title>Abstract</jats:title><jats:p>Extracellular vesicles (EVs) have been considered to deliver biological cargos betweencells and mediate intercellular communication. However, the mechanisms that underlie the biological process of EV uptake and cytoplasmic cargo release in recipient cells are largely unknown. Quantitative and real-time assays for assessment of the cargo delivery efficiency inside recipient cells have not been feasible. In this study, we developed an EV cargo delivery (EVCD) assay using a split luciferase called the NanoBiT system. Recipient cells expressing LgBiT, a large subunit of luciferase, emit luminescence when the EV cargo proteins fused with a small luminescence tag (HiBiT tag) that can complement LgBiT are delivered to the cytoplasm of recipient cells. Using the EVCD assay, the cargo delivery efficiency of EVs could be quantitatively measured in real time. This assay was highly sensitive in detecting a single event of cargo delivery per cell. We found that modification of EVs with a virus-derived fusogenic protein significantly enhanced the cytoplasmic cargo delivery; however, in the absence of a fusogenic protein, the cargo delivery efficiency of EVs was below the threshold of the assay. The EVCD assay could assess the effect of entry inhibitors on EV cargo delivery. Furthermore, using a luminescence microscope, the cytoplasmic cargo delivery of EVs was directly visualized in living cells. This assay could reveal the biological mechanism of the cargo delivery processes of EVs.</jats:p>
Virus-mimicking nanocarriers for the intracellular delivery of therapeutic biomolecules. International-journal

Masaharu Somiya, Shun'ichi Kuroda

Nanomedicine (London, England)　15　(12)　1163-1165　2020/05

DOI： 10.2217/nnm-2020-0078 　
Where does the cargo go?: Solutions to provide experimental support for the “extracellular vesicle cargo transfer hypothesis” International-journal Peer-reviewed

Somiya, M.

Journal of Cell Communication and Signaling　14　(2)　135-146　2020

DOI： 10.1007/s12079-020-00552-9 　
DDS Nanocarriers Mimicking Early Infection Machinery of Viruses Peer-reviewed

Somiya, M., Kuroda, S.

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan　140　(2)　147-152　2020

DOI： 10.1248/yakushi.19-00187-2 　
Construction of a Macrophage-Targeting Bio-nanocapsule-Based Nanocarrier International-journal Peer-reviewed

Li, H., Somiya, M., Tatematsu, K., Kuroda, S.

Methods in Molecular Biology　2059　299-313　2020

DOI： 10.1007/978-1-4939-9798-5_16 　

ISSN： 1064-3745
Induction of lipid droplets in non-macrophage cells as well as macrophages by liposomes and exosomes International-journal Peer-reviewed

Fujita, K., Somiya, M., Kuroda, S., Hinuma, S.

Biochemical and Biophysical Research Communications　510　(1)　184-190　2019

DOI： 10.1016/j.bbrc.2019.01.078 　
Oriented immobilization to nanoparticles enhanced the therapeutic efficacy of antibody drugs International-journal Peer-reviewed

Iijima, M., Araki, K., Liu, Q., Somiya, M., Kuroda, S.

Acta Biomaterialia　86　373-380　2019

DOI： 10.1016/j.actbio.2019.01.011 　
In vivo uterine local gene delivery system using TAT-displaying bionanocapsules International-journal Peer-reviewed

Koizumi, K., Nakamura, H., Iijima, M., Matsuzaki, T., Somiya, M., Kumasawa, K., Kimura, T., Kuroda, S.

Journal of Gene Medicine　21　(12)　e3140　2019
Publisher: Wiley
DOI： 10.1002/jgm.3140 　

ISSN： 1099-498X
A hepatitis B virus-derived human hepatic cell-specific heparin-binding peptide: Identification and application to a drug delivery system International-journal Peer-reviewed

Liu, Q., Somiya, M., Iijima, M., Tatematsu, K., Kuroda, S.

Biomaterials Science　7　(1)　322-335　2019
Publisher: Royal Society of Chemistry ({RSC})
DOI： 10.1039/c8bm01134f 　

ISSN： 2047-4830
CD11c-specific bio-nanocapsule enhances vaccine immunogenicity by targeting immune cells International-journal Peer-reviewed

Matsuo, H., Somiya, M., Iijima, M., Arakawa, T., Kuroda, S.

Journal of Nanobiotechnology　16　(1)　59-59　2018

DOI： 10.1186/s12951-018-0386-6 　
Development of a macrophage-targeting and phagocytosis-inducing bio-nanocapsule-based nanocarrier for drug delivery International-journal Peer-reviewed

Li, H., Tatematsu, K., Somiya, M., Iijima, M., Kuroda, S.

Acta Biomaterialia　73　412-423　2018
Publisher: Acta Materialia Inc
DOI： 10.1016/j.actbio.2018.04.023 　

ISSN： 1878-7568 1742-7061
Low immunogenic bio-nanocapsule based on hepatitis B virus escape mutants International-journal Peer-reviewed

Jung, J., Somiya, M., Jeong, S.-Y., Choi, E.K., Kuroda, S.

Nanomedicine: Nanotechnology, Biology, and Medicine　14　(2)　595-600　2018
Publisher: Elsevier Inc.
DOI： 10.1016/j.nano.2017.11.017 　

ISSN： 1549-9642 1549-9634
生物の仕組みに学ぶDDSナノキャリアの開発

曽宮正晴

Drug Delivery System　32　(2)　156-157　2017/03
Publisher: 日本DDS学会
ISSN： 0913-5006
Current progress of virus-mimicking nanocarriers for drug delivery International-journal Peer-reviewed

Somiya, M., Liu, Q., Kuroda, S.

Nanotheranostics　1　(4)　415-429　2017
Publisher: Ivyspring International Publisher
DOI： 10.7150/ntno.21723 　

ISSN： 2206-7418
Drug delivery application of extracellular vesicles; insight into production, drug loading, targeting, and pharmacokinetics Peer-reviewed

Takahiro Ochiya, Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan, Masaharu Somiya, Yusuke Yoshioka

AIMS Bioengineering　4　(1)　73-92　2017
Publisher: American Institute of Mathematical Sciences ({AIMS})
DOI： 10.3934/bioeng.2017.1.73 　
Biomimetic strategy for development of pleiotropic DDS carriers Peer-reviewed

Somiya, M.

Drug Delivery System　32　(2)　156-157　2017
Publisher: Japan Society of Drug Delivery System
DOI： 10.2745/dds.32.156 　

ISSN： 1881-2732 0913-5006
【がんのバイオマーカー】血中エクソソームによるがん診断の可能性

曽宮正晴, 吉岡祐亮

血液フロンティア　26　(10)　1379-1384　2016/09
Publisher: (株)医薬ジャーナル社
ISSN： 1344-6940
Release of siRNA from Liposomes Induced by Curcumin Peer-reviewed

Fujita, K., Hiramatsu, Y., Minematsu, H., Somiya, M., Kuroda, S., Seno, M., Hinuma, S.

Journal of Nanotechnology　2016　1-6　2016
Publisher: Hindawi Publishing Corporation
DOI： 10.1155/2016/7051523 　

ISSN： 1687-9511 1687-9503
Elucidation of the early infection machinery of hepatitis B virus by using bio-nanocapsule International-journal Peer-reviewed

Liu, Q., Somiya, M., Kuroda, S.

World Journal of Gastroenterology　22　(38)　8489-8489　2016

DOI： 10.3748/wjg.v22.i38.8489 　

ISSN： 1007-9327

eISSN： 2219-2840
Cellular uptake of hepatitis B virus envelope L particles is independent of sodium taurocholate cotransporting polypeptide, but dependent on heparan sulfate proteoglycan International-journal Peer-reviewed

Somiya, M., Liu, Q., Yoshimoto, N., Iijima, M., Tatematsu, K., Nakai, T., Okajima, T., Kuroki, K., Ueda, K., Kuroda, S.

Virology　497　23-32　2016

DOI： 10.1016/j.virol.2016.06.024 　

ISSN： 0042-6822
Potential of a non-cationic liposomes-based delivery system for nucleic acid medicines

Somiya, M., Kuroda, S.

Drug Delivery System　31　(1)　35-43　2016
Publisher: Japan Society of Drug Delivery System
DOI： 10.2745/dds.31.35 　

ISSN： 1881-2732 0913-5006
Mutational analysis of hepatitis B virus pre-S1 (9-24) fusogenic peptide International-journal Peer-reviewed

Liu, Q., Somiya, M., Shimada, N., Sakamoto, W., Yoshimoto, N., Iijima, M., Tatematsu, K., Nakai, T., Okajima, T., Maruyama, A., Kuroda, S.

Biochemical and Biophysical Research Communications　474　(2)　406-412　2016

DOI： 10.1016/j.bbrc.2016.04.125 　

ISSN： 0006-291X

eISSN： 1090-2104
One-step scalable preparation method for non-cationic liposomes with high siRNA content Peer-reviewed

Somiya, Masaharu, Yamaguchi, Kotomi, Liu, Qiushi, Niimi, Tomoaki, Maturana, Andr{\'{e } }s Daniel, Iijima, Masumi, Yoshimoto, Nobuo, Kuroda, Shun'ichi

Int. J. Pharm.　490　(1-2)　316-323　2015/07

DOI： 10.1016/j.ijpharm.2015.05.072 　

ISSN： 0378-5173

eISSN： 1873-3476
Virosomes of hepatitis B virus envelope L proteins containing doxorubicin: synergistic enhancement of human liver-specific antitumor growth activity by radiotherapy Peer-reviewed

Qiushi Liu, Joohee Jung, Masaharu Somiya, Masumi Iijima, Nobuo Yoshimoto, Tomoaki Niimi, Andres D. Maturana, Seol Hwa Shin, Seong-Yun Jeong, Eun Kyung Choi, Shun'ichi Kuroda

INTERNATIONAL JOURNAL OF NANOMEDICINE　10　4159-4172　2015

DOI： 10.2147/IJN.S84295 　

ISSN： 1178-2013
Intracellular trafficking of bio-nanocapsule-liposome complex: Identification of fusogenic activity in the pre-S1 region of hepatitis B virus surface antigen L protein Peer-reviewed

Somiya, M., Sasaki, Y., Matsuzaki, T., Liu, Q., Iijima, M., Yoshimoto, N., Niimi, T., Maturana, A.D., Kuroda, S.

Journal of Controlled Release　212　10-8　2015

DOI： 10.1016/j.jconrel.2015.06.012 　

ISSN： 0168-3659

eISSN： 1873-4995
Virosomes of hepatitis B virus envelope L proteins containing doxorubicin: synergistic enhancement of human liver-specific antitumor growth activity by radiotherapy. International-journal Peer-reviewed

Qiushi Liu, Joohee Jung, Masaharu Somiya, Masumi Iijima, Nobuo Yoshimoto, Tomoaki Niimi, Andrés D Maturana, Seol Hwa Shin, Seong-Yun Jeong, Eun Kyung Choi, Shun'ichi Kuroda

International journal of nanomedicine　10　4159-72　2015
Publisher: Dove Medical Press Ltd.
DOI： 10.2147/IJN.S84295 　

ISSN： 1178-2013 1176-9114
Development of a virus-mimicking nanocarrier for drug delivery systems: The bio-nanocapsule International-journal Peer-reviewed

Somiya, M., Kuroda, S.

Advanced Drug Delivery Reviews　95　77-89　2015

DOI： 10.1016/j.addr.2015.10.003 　

ISSN： 0169-409X

eISSN： 1872-8294
リポソームの最新動向バイオナノカプセル‐リポソーム複合体の生体内ピンポイント薬剤送達への応用

曽宮正晴, 良元伸男, 黒田俊一

月刊ファインケミカル　42　(4)　44-49　2013/04/15
Publisher:
ISSN： 0913-6150
Nano-visualization of oriented-immobilized IgGs on immunosensors by high-speed atomic force microscopy Peer-reviewed

Masumi Iijima, Masaharu Somiya, Nobuo Yoshimoto, Tomoaki Niimi, Shun'ichi Kuroda

SCIENTIFIC REPORTS　2　790　2012/11

DOI： 10.1038/srep00790 　

ISSN： 2045-2322
Targeting of polyplex to human hepatic cells by bio-nanocapsules, hepatitis B virus surface antigen L protein particles Peer-reviewed

Masaharu Somiya, Nobuo Yoshimoto, Masumi Iijima, Tomoaki Niimi, Takehisa Dewa, Joohee Jung, Shun'ichi Kuroda

BIOORGANIC & MEDICINAL CHEMISTRY　20　(12)　3873-3879　2012/06

DOI： 10.1016/j.bmc.2012.04.031 　

ISSN： 0968-0896

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Misc. 4

Development of Drug Delivery System Nanocarrier by Biomimicking Technology : Bio-Nanocapsule Based on Hepatitis B Virus Early Infection Machinery

45　(11)　18-24　2016/11
Publisher: シーエムシー出版
ISSN： 0913-6150
3P-223 Generation of Hepatitis B Virus Envelope L Particle-derived Virosomes Containing Doxorubicin

Liu Qiushi, Somiya Masaharu, Kuroda Shun'ichi

67　326-326　2015
Publisher: 日本生物工学会
3P-239 Non-cationic bio-nanocapsule-based nanocarrier for siRNA delivery

Yamaguchi Kotomi, Somiya Masaharu, Kuroda Shun'ichi

66　254-254　2014
Publisher: 日本生物工学会
3P-240 Dendritic cell-specific antigen delivery by bio-nanocapsule-liposome complex

Yokoi Sakiho, Somiya Masaharu, Matsuo Hidenori, Kuroda Shun'ichi

66　254-254　2014
Publisher: 日本生物工学会

Presentations 12

3P-223 Generation of Hepatitis B Virus Envelope L Particle-derived Virosomes Containing Doxorubicin

Liu Qiushi, Somiya Masaharu, Kuroda Shun'ichi

日本生物工学会大会講演要旨集　2015/09/25
B型肝炎ウイルスの感染機構を模倣したバイオナノカプセル‐リポソーム複合体のエンドソーム脱出機構の解明

曽宮正晴, 曽宮正晴, 曽宮正晴, 劉秋実, 劉秋実, 黒田俊一, 黒田俊一

日本DDS学会学術集会プログラム予稿集　2015/06/12
B型肝炎ウイルスの感染機構を搭載したDDSナノキャリアのがん治療への応用

曽宮正晴, 山口琴美, 黒田俊一

日本薬学会年会要旨集(CD-ROM)　2015
3P-240 Dendritic cell-specific antigen delivery by bio-nanocapsule-liposome complex

Yokoi Sakiho, Somiya Masaharu, Matsuo Hidenori, Kuroda Shun'ichi

日本生物工学会大会講演要旨集　2014/08/05
3P-239 Non-cationic bio-nanocapsule-based nanocarrier for siRNA delivery

Yamaguchi Kotomi, Somiya Masaharu, Kuroda Shun'ichi

日本生物工学会大会講演要旨集　2014/08/05
3P-238 Endocytosis-independent cytoplasm-specific delivery by bio-nanocapsuleliposome complex

Somiya Masaharu, Kuroda Shun'ichi

日本生物工学会大会講演要旨集　2014/08/05
バイオナノカプセル‐リポソーム複合体による抗がん剤(ドキソルビシン)のヒト肝臓由来組織への能動的送達

劉秋実, 仲本拓央, 曽宮正晴, 飯嶋益巳, 黒田俊一

日本DDS学会学術集会プログラム予稿集　2014/07/01
抗体分子の整列提示能及びクラスタリング能を有するナノキャリア「バイオナノカプセル」を用いた抗体医薬を機能向上させる新ストラテジー

荒木響子, 劉秋実, 曽宮正晴, 飯嶋益巳, 黒田俊一

日本分子生物学会年会プログラム・要旨集(Web)　2014
ヒトEGFR抗体提示型バイオナノカプセルの細胞内侵入機構の解析

荒木響子, 曽宮正晴, 黒田俊一

日本DDS学会学術集会プログラム予稿集　2013/06/05
バイオナノカプセル複合体化によるポリプレックスの再標的化

曽宮正晴, 良元伸男, 黒田俊一

日本DDS学会学術集会プログラム予稿集　2012/06/05
バイオナノカプセル‐ポリプレックス複合体の遺伝子導入能

曽宮正晴, 黒田俊一

日本分子生物学会年会プログラム・要旨集(Web)　2011
ヒト細胞株SC‐01MFPにおけるタンパク質生産の特性評価

曽宮正晴, 中村繁樹, 井上愛子, 井上祐一, 川原浩治

日本農芸化学会大会講演要旨集　2010/03/05

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Industrial Property Rights 1

核酸を内封してなる中性又はアニオン性リポソーム及びその製造方法。

黒田俊一, 曽宮正晴

Property Type: Patent

Research Projects 15

生体膜編集技術の基盤構築

曽宮正晴

Offer Organization: 日本学術振興会

System: 科学研究費助成事業

Category: 基盤研究(B)

Institution: 大阪大学

2026/04/01 - 2029/03/31
Construction of designer cells by synthetic membrane fusion machinery

Offer Organization: Japan Science and Technology Agency (JST)

System: PRESTO

2024/09 - 2028/03
Computational design of de novo fusogens

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Transformative Research Areas (A)

Institution: The University of Osaka

2025/04/01 - 2027/03/31
タンパク質設計による新規ウイルス様ベクターの開発

曽宮正晴

Offer Organization: アステラス病態代謝研究会

System: 2024年度研究助成

2025/01 - 2026/12
エクソソームの改変による新規遺伝子治療ベクターの開発

曽宮正晴

Offer Organization: テルモ生命科学振興財団

System: 2024年度研究助成金

2024/11 - 2026/03
Deciphering the intercellular signaling via extracellular vesicles by lipid-recognizing GPCRs

Somiya Masaharu

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Early-Career Scientists

Category: Grant-in-Aid for Early-Career Scientists

Institution: Osaka University

2020/04/01 - 2022/03/31

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Extracellular vesicles (EVs) have been known to involve in intercellular communications by delivering cargo molecules. In this study, we identified the novel mechanism of EV-mediated intercellular communication via the interaction between the lipid moiety of EVs and cell surface receptor, G protein-coupled receptors (GPCRs). By using the library of engineered GPCRs that include over 300 human GPCRs, we found multiple candidate GPCRs possibly recognize the lipid moiety of EVs. Those GPCRs may recognize the lipids of EVs and induce intracellular signaling.
Development of Neo-bionanocapsule for Various In Vivo Targets

KURODA SHUN'ICHI

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (S)

Category: Grant-in-Aid for Scientific Research (S)

Institution: Osaka University

2016/05/31 - 2021/03/31

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We have identified the functional domains that have been acquired by viruses (natural DDS (drug delivery system) nanocarriers) during the evolutionary process, such as 1) strong stealth to escape elimination by the immune system,2) high active targeting to target organs/cells, 3) efficient entry into target cells, and 4) intracytoplasmic transfer of drugs to exert their medicinal effects. We have developed novel DDS nanocarrier with these capabilities for precise in vivo spatiotemporal control of drugs. In addition, we have developed related technologies, such as efficient selection method of targeted molecules and precise presentation methods on the carrier surface.
mRNA sorting into exosomes and its application for drug delivery Competitive

Somiya Masaharu

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Early-Career Scientists

Category: Grant-in-Aid for Early-Career Scientists

Institution: Osaka University

2018/04/01 - 2020/03/31

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First, encapsulation of mRNA into exosomes by using exosome protein-binding aptamer was not successful for unknown reason. Then we switched the strategy to use viral proteins to encapsulate specific mRNA into exosomes. Bu using this method, it was confirmed that mRNA was encapsulated into exosomes and secreted. The mRNA-encapsulated exosomes were internalized by recipient cells and reporter gene was functionally delivered. Furthermore, mRNA expression in the recipient cells can be controlled by small molecules by combining mRNA and RNA aptamer technology.
Cancer therapy utilizing nucleic acid-encapsulating exosomes that target tumor-associated macrophages Competitive

Masaharu Somiya

Offer Organization: JSPS

System: Grant-in-Aid for JSPS Fellows

2017/04/26 - 2020/03/31
牛乳に含まれる細胞外小胞をヒト細胞が認識し応答する分子機構の解明 Competitive

曽宮正晴

Offer Organization: 乳の学術連合「牛乳乳製品健康科学会議」

System: 2019年度「牛乳乳製品健康科学」学術研究

2019/04 - 2020/03
Research Grant Competitive

Masaharu Somiya

Offer Organization: JGC-S Scholarship Foundation

2018/09 - 2019/08
Discovery of Novel Therapeutics in Kidney Cancer Competitive

Masaharu Somiya

Offer Organization: AMED

System: Interstellar Initiative 2018

2018/08 - 2019/03
乳中に含まれるエクソソームの機能性成分の同定とそのメカニズム解明 Competitive

曽宮正晴

Offer Organization: 三島海雲記念財団

System: 平成29年度学術研究奨励金

2017/07 - 2018/06
アルブミン結合ペプチドによる核酸医薬品のアルブミン製剤化技術の開発 Competitive

曽宮正晴

Offer Organization: 大阪大学国際医工情報センター

System: MEIグラント、グラントB

2017/12 - 2018/03
細胞内動態を制御した効率的なＢ型肝炎ウイルス由来薬剤送達ナノキャリアの開発 Competitive

曽宮正晴

Offer Organization: 日本学術振興会

System: 科学研究費助成事業特別研究員奨励費

Category: 特別研究員奨励費

Institution: 名古屋大学

2013/04/01 - 2016/03/31

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B型肝炎ウイルス(HBV)由来ペプチドの膜融合活性をペプチド提示リポソームの機能解析を行った結果、ペプチド中の特定のアミノ酸残基の働きによりpH感受性を示すことが明らかとなった。また、HBV由来ナノ粒子、バイオナノカプセル(BNC)の低pH依存性の膜融合活性が、脂質二重膜の組成に大きく影響されることが明らかとなった。BNCの膜融合に必要なのは、脂質二重膜中のコレステロールの存在と、脂質の脂肪酸鎖が飽和していること、の2点である事が示された。また、HBVの感染機構を、バイオナノカプセル(BNC)を使用して解析した。まずBNCに、HBVに存在している翻訳後修飾を化学的に施した。その結果、化学修飾をしたBNCでのみ、HBVの受容体であるsodium taurocholate cotransporting polypeptide (NTCP)と結合できるようになった。この修飾BNCを使用して、NTCP発現ヒト肝臓細胞株HepG2への取り込み効率を解析した。その結果、HBV受容体NTCPは細胞表面ではHBVとの結合に関与せず、細胞内部でHBV受容体として働いていることが示唆された。細胞内への取り込みは、ヘパラン硫酸プロテオグリカン(HSPG)と呼ばれる別のタンパク質が担当していることが判明した。つまり、細胞表面のHSPGと結合した化学修飾BNCは、エンドサイトーシスによって細胞内へ取り込まれた後、エンドソーム内に存在しているNTCPと結合することによってその後の感染プロセスが進行するという事が示唆された。また、作製した化学修飾BNCは、HBVの感染を抑制することが判明しており、BNCがHBV侵入阻害剤として使用できること、またBNCを使用して、更なるHBV感染機構の解明が期待できることが示唆された。作製した化学修飾BNCは、抗HBV薬を探索する際のプローブとして、共同研究先で使用されており、候補化合物のスクリーニングが行われている。これらの研究内容は、現在英文雑誌に投稿中である。

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