Article
Oncology
Ryosuke Ono, Kosuke Takayama, Rika Onishi, Sora Tokuoka, Fuminori Sakurai, Hiroyuki Mizuguchi
Summary: This study aimed to evaluate the potential of oncolytic adenoviruses as a treatment for pancreatic cancer. They found that the commonly used adenovirus serotype 5 (Ad5) had limitations due to decreased receptor expression and neutralizing antibodies. As an alternative, an adenovirus serotype 35 (Ad35) was developed, which recognized a specific receptor on pancreatic cancer cells and had fewer neutralizing antibodies.
ANTICANCER RESEARCH
(2023)
Article
Virology
Minzhi Gong, Yating Wang, Shijia Liu, Boshuo Li, Enqi Du, Yupeng Gao
Summary: Adenovirus vectors have a wide range of applications in infectious disease research and gene therapy. In this study, a FAdV-4 infectious clone was successfully constructed and the biological pathology of FAdV-4 was clarified. Single-cycle adenovirus vectors were also constructed by deleting the IIIa capsid cement protein gene.
Article
Neurosciences
David Goertsen, Nicholas C. Flytzanis, Nick Goeden, Miguel R. Chuapoco, Alexander Cummins, Yijing Chen, Yingying Fan, Qiangge Zhang, Jitendra Sharma, Yangyang Duan, Liping Wang, Guoping Feng, Yu Chen, Nancy Y. Ip, James Pickel, Viviana Gradinaru
Summary: The study developed AAV capsids that achieved robust transgene expression in the brain with decreased liver targeting after non-invasive administration, enabling more targeted systemic gene delivery. This organ-specific targeting extends to marmosets, allowing for non-invasive gene delivery with distinct transgene expression patterns. The ability to cross the blood-brain barrier with neuronal specificity in rodents and non-human primates opens up new avenues for basic research and therapeutic possibilities beyond naturally occurring serotypes.
NATURE NEUROSCIENCE
(2022)
Article
Oncology
Ryosuke Ono, Kosuke Takayama, Fuminori Sakurai, Hiroyuki Mizuguchi
Summary: The study developed a novel OAd fully composed of OAd35, which recognizes CD46 as an infection receptor and showed efficient cell lysis activities similar to OAd5 in CAR-positive tumor cells, while exhibiting higher levels of cell lysis activities than OAd5 in CAR-negative tumor cells. OAd35 had lower proportions of neutralizing antibodies in adults compared to Ad5.
MOLECULAR THERAPY-ONCOLYTICS
(2021)
Article
Medicine, Research & Experimental
Chang Li, Hongjie Wang, Sucheol Gil, Audrey Germond, Connie Fountain, Audrey Baldessari, Jiho Kim, Zhinan Liu, Aphrodite Georgakopoulou, Stefan Radtke, Tamas Rasko, Amit Pande, Christina Chiang, Eli Chin, Evangelia Yannaki, Zsuzsanna Izsvak, Thalia Papayannopoulou, Hans-Peter Kiem, Andre Lieber
Summary: This study tested a new approach for in vivo hematopoietic stem cell transduction/selection in rhesus macaques. The results showed successful transduction of HSCs and increased levels of gamma-globin expressing red blood cells. Pre-treatment with dexamethasone and interleukin receptor blockers successfully blunted proinflammatory cytokine activation. The findings demonstrate the feasiblity of in vivo HSC gene therapy in humans without high-dose chemotherapy and HSC transplantation.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2022)
Article
Biotechnology & Applied Microbiology
Eloise Hudry, Fumiaki Aihara, Emily Meseck, Keith Mans, Cameron McElroy, Deepa Chand, Francis Fonyuy Tukov, Kelley Penraat
Summary: Hepatotoxicity associated with intravenous/intrathecal adeno-associated virus (AAV) gene therapy has been observed in preclinical species and patients. The current study characterizes key aspects of AAV-induced hepatotoxicity in nonhuman primates, highlighting the usefulness of this nonclinical species for studying liver injury.
Article
Gastroenterology & Hepatology
Daniel Stone, Nadja Meumann, Anne-Sophie Kuhlmann, Christopher W. Peterson, Hong Xie, Pavitra Roychoudhury, Michelle A. Loprieno, Xuan-Khang Vu, Daniel E. Strongin, Elizabeth J. Kenkel, Anoria Haick, Laurence Stensland, Willimark M. Obenza, Jacob Parrott, Veronica Nelson, Robert D. Murnane, Meei-Li Huang, Martine Aubert, Hans-Peter Kiem, Hildegard Buening, Keith R. Jerome
Summary: In order to optimize the AAV vector selection process, a multiplex barcoding approach was developed to simultaneously evaluate the in vivo performance of various AAV vectors in multiple organs. The findings showed differences in biodistribution and tissue transduction patterns among animals, influenced by their distinctive serological status.
HEPATOLOGY COMMUNICATIONS
(2023)
Article
Microbiology
Juan M. Bustamante, Brooke E. White, Gregory K. Wilkerson, Carolyn L. Hodo, Lisa D. Auckland, Wei Wang, Stephanie McCain, Sarah A. Hamer, Ashley B. Saunders, Rick L. Tarleton
Summary: This study demonstrates that higher dose, intermittent administration of benznidazole can effectively treat Trypanosoma cruzi infection. Administration twice a week, for more than 4 months, provides the best chance for parasitological cure.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Gastroenterology & Hepatology
Nadja Meumann, Marti Cabanes-Creus, Moritz Ertelt, Renina Gale Navarro, Julie Lucifora, Qinggong Yuan, Karin Nien-Huber, Ahmed Abdelrahman, Xuan-Khang Vu, Liang Zhang, Ann-Christin Franke, Christian Schmithals, Albrecht Piiper, Annabelle Vogt, Maria Gonzalez-Carmona, Jochen T. Frueh, Evelyn Ullrich, Philip Meuleman, Steven R. Talbot, Margarete Odenthal, Michael Ott, Erhard Seifried, Clara T. Schoeder, Joachim Schwable, Leszek Lisowski, Hildegard Buning
Summary: This article reports two gene vector variants, MLIV.K and MLIV.A, which were obtained through in vivo AAV peptide display selection in mice. They showed improved hepatocyte targeting and transduction efficiency compared to AAV2 and AAV8, and have potential for liver disease treatment.
Article
Ophthalmology
Anita Grover, Sethu Sankaranarayanan, Vidhu Mathur, Poojan Suri, Haiyan Qiu, Yaisa Andrews-Zwilling, Kirsten Mease, Lori K. Taylor, Ellen Cahir-McFarland, Sanjay Keswani, Ted Yednock
Summary: ANX007 is an antibody that blocks the binding of C1q and inhibits the classical complement cascade. It has potential therapeutic effects for neurodegenerative ophthalmic diseases. Experimental studies showed that ANX007 can target and engage with C1q in the retina, supporting its further clinical evaluation.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2023)
Article
Oncology
Aleksei A. Stepanenko, Anastasiia O. Sosnovtseva, Marat P. Valikhov, Anastasia A. Chernysheva, Sergey A. Cherepanov, Gaukhar M. Yusubalieva, Zsolt Ruzsics, Anastasiia Lipatova, Vladimir P. Chekhonin
Summary: Ad5-delta-24-RGD is the most clinically advanced recombinant adenovirus for glioma therapy. Different fiber-modified rAds were constructed and compared, showing that Ad5/35-delta-24 and Ad5/3-delta-24 exhibited superior infectivity and cytolytic efficacy compared to Ad5-delta-24-RGD. The expression of adenoviral receptors/coreceptors and integrins did not predict the cytolytic efficacy of the fiber-modified rAds. CT-2A and GL261 glioma cells were identified as murine cell models for studying fiber chimeric rAds. Ad5/35-delta-24 armed with the immune costimulator OX40L demonstrated potential for glioblastoma treatment.
MOLECULAR THERAPY-ONCOLYTICS
(2022)
Article
Virology
Robin Nilson, Olivia Luebbers, Linus Weiss, Karmveer Singh, Karin Scharffetter-Kochanek, Markus Rojewski, Hubert Schrezenmeier, Philip Helge Zeplin, Wolfgang Funk, Lea Krutzke, Stefan Kochanek, Astrid Kritzinger
Summary: This study introduces several enhancers that greatly improve the efficiency of HAdV-5-mediated gene transfer in hMSCs derived from bone marrow and adipose tissue. The migration behavior of hMSCs treated with enhancers was not affected, which is essential for many therapeutic applications. Enhancer-mediated HAdV-5 vector transduction is a valuable method for engineering hMSCs and developing innovative hMSC therapeutics.
Article
Biotechnology & Applied Microbiology
Bishnu P. De, Jonathan B. Rosenberg, Nithya Selvan, Isabelle Wilson, Nadir Yusufzai, Alessandria Greco, Stephen M. Kaminsky, Linda A. Heier, Rodolfo J. Ricart Arbona, Ileana C. Miranda, Sebastien Monette, Anju Nair, Richie Khanna, Ronald G. Crystal, Dolan Sondhi
Summary: CLN2 disease is a childhood genetic disorder caused by mutations in the CLN2 gene, resulting in neurodegeneration. The study found that intracisternal delivery of AAVrh.10hCLN2 can safely distribute therapeutic TPP-1 throughout the brain and cerebrospinal fluid at potentially therapeutic levels.
HUMAN GENE THERAPY
(2023)
Article
Immunology
Seung-Phil Shin, Kwang-Soo Shin, Jeong-Mi Lee, In-Kyung Jung, Jimo Koo, Seung-Woo Lee, Seowoo Park, Jieun Shin, Myunghwan Park, Bongju Park, Hanseul Oh, Bon-Sang Koo, Jungjoo Hong, Choong-Min Ryu, Jae-Ouk Kim, Taegwon Oh, Chang-Yuil Kang
Summary: The study presents the development of AdCLD-CoV19 platform, which can boost humoral and cellular immunity with a single vaccination, effectively preventing SARS-CoV-2. The platform demonstrates the ability to neutralize various SARS-CoV-2 variants, and the neutralizing antibody activity can be restored through booster shots.
Article
Biotechnology & Applied Microbiology
Charles-Antoine Coupet, Clarisse Dubois, Alexei Evlachev, Nadine Kehrer, Marie Baldazza, Sam Hofman, Michel Vierboom, Perrine Martin, Genevieve Inchauspe
Summary: This study demonstrates the safety and activity of MVA-hIL-7-Fc in nonhuman primates as a potential treatment for sepsis. The treatment showed functionality in stimulating the immune system and resulted in changes in circulating immune cells.
HUMAN VACCINES & IMMUNOTHERAPEUTICS
(2022)
Article
Oncology
Keisaku Wakabayashi, Fuminori Sakurai, Ryosuke Ono, Toshiyoshi Fujiwara, Hiroyuki Mizuguchi
ANTICANCER RESEARCH
(2020)
Article
Pharmacology & Pharmacy
Ryosuke Negoro, Kanae Kawai, Moe Ichikawa, Sayaka Deguchi, Kazuo Takayama, Hiroyuki Mizuguchi
DRUG METABOLISM AND PHARMACOKINETICS
(2020)
Article
Biotechnology & Applied Microbiology
Nobuhiko Kanaya, Shinji Kuroda, Yoshihiko Kakiuchi, Kento Kumon, Tomoko Tsumura, Masashi Hashimoto, Toshiaki Morihiro, Tetsushi Kubota, Katsuyuki Aoyama, Satoru Kikuchi, Masahiko Nishizaki, Shunsuke Kagawa, Hiroshi Tazawa, Hiroyuki Mizuguchi, Yasuo Urata, Toshiyoshi Fujiwara
Article
Multidisciplinary Sciences
Yukiko Toba, Sayaka Deguchi, Natsumi Mimura, Ayaka Sakamoto, Kazuo Harada, Kazumasa Hirata, Kazuo Takayama, Hiroyuki Mizuguchi
Article
Pharmacology & Pharmacy
Kazuo Takayama, Kohei Ito, Akiko Matsui, Tomoki Yamashita, Kentaro Kawakami, Daisuke Hirayama, Wataru Kishimoto, Hiroshi Nakase, Hiroyuki Mizuguchi
Summary: In this study, gene expression profiles related to drug absorption, distribution, metabolism, and excretion were analyzed in biopsy samples from different regions of the intestine of patients with inflammatory bowel disease. The study found significant differences in gene expression levels across different regions of the intestine, particularly in drug-metabolizing enzymes and drug transporters. This information may be crucial for accurately predicting the pharmacokinetics of orally administered drugs.
DRUG METABOLISM AND DISPOSITION
(2021)
Article
Immunology
Kahori Shimizu, Fuminori Sakurai, Shunsuke Iizuka, Ryosuke Ono, Tomohito Tsukamoto, Fumitaka Nishimae, Shin-Ichiro Nakamura, Toru Nishinaka, Tomoyuki Terada, Yasushi Fujio, Hiroyuki Mizuguchi
Summary: Adenovirus vectors can cause hepatotoxicity in two phases post-administration, with early phase involving inflammatory cytokines. The modified Ad vector, Ad-E4-122aT-CAL2, significantly suppresses leaky Ad gene expression in the liver, leading to reduced acute hepatotoxicity. IL-6 induced by Ad vectors enhances leaky Ad gene expression and cytotoxicity, but this effect is attenuated by the presence of Ad-E4-122aT-CAL2.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Medicine, Research & Experimental
Moe Ichikawa, Ryosuke Negoro, Kanae Kawai, Tomoki Yamashita, Kazuo Takayama, Hiroyuki Mizuguchi
Summary: The study demonstrated that vinblastine treatment can effectively remove residual undifferentiated hiPSCs in hiPSC-IECs, leading to decreased pluripotent marker expression and increased intestinal marker expression. The viability of undifferentiated hiPSCs was significantly reduced by vinblastine treatment. MDR1-negative cells, such as undifferentiated hiPSCs, were found to die upon vinblastine treatment due to their inability to excrete the drug, suggesting that vinblastine-treated hiPSC-IECs could be a safe and effective cell source for regenerative medicine.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2021)
Article
Oncology
Ryosuke Ono, Kosuke Takayama, Fuminori Sakurai, Hiroyuki Mizuguchi
Summary: The study developed a novel OAd fully composed of OAd35, which recognizes CD46 as an infection receptor and showed efficient cell lysis activities similar to OAd5 in CAR-positive tumor cells, while exhibiting higher levels of cell lysis activities than OAd5 in CAR-negative tumor cells. OAd35 had lower proportions of neutralizing antibodies in adults compared to Ad5.
MOLECULAR THERAPY-ONCOLYTICS
(2021)
Article
Oncology
Fuminori Sakurai, Fumitaka Nishimae, Kosuke Takayama, Hiroyuki Mizuguchi
Summary: This study examined five types of oncolytic adenoviruses (OAds) containing different types of E1 gene expression cassettes, and found that OAd-Delta 24, with a 24-bp deletion in the E1A gene, demonstrated the most efficient oncolytic activities against human tumor cell lines, despite slightly higher cytotoxicity to normal human cells compared to other OAds. These results provide important insights for the development of safe and effective OAds.
ANTICANCER RESEARCH
(2021)
Article
Virology
Chieko Inoue, Ryosuke Negoro, Kazuo Takayama, Hiroyuki Mizuguchi, Fuminori Sakurai
Summary: This study demonstrates that hiPS-SIECs are a promising in vitro model for evaluating virus infection, with differences observed in replication and immune responses of reovirus in these cells under different infection methods.
Article
Chemistry, Analytical
Menglu Li, Yukiko Ueyama-Toba, Matthew Lindley, Gunganist Kongklad, Yasunori Nawa, Yasuaki Kumamoto, Seiichi Ishida, Yasunari Kanda, Satoshi Fujita, Hiroyuki Mizuguchi, Katsumasa Fujita
Summary: To promote the clinical application of hiPSC-derived hepatocytes, a label-free Raman microscopy method is used to monitor regenerative processes and assess differentiation efficiency. The method has successfully identified intracellular biomolecules in live samples and compared the phenotypes of hiPSC-derived hepatocytes with HepaRG and commercially available iCell hepatocytes. The study also explored the use of Raman imaging as a hepatotoxicity assay, demonstrating its potential for quality control and hepatotoxicity screening.
ANALYTICAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Jumpei Inui, Yukiko Ueyama-Toba, Seiji Mitani, Hiroyuki Mizuguchi
Summary: A method has been developed to dissociate, cryopreserve, and reseed human induced pluripotent stem cell-derived hepatocyte-like cells (HLCs) without loss of their functions. This technology enables the availability of cryopreserved HLCs for drug discovery research.
Article
Biology
Eiko Sakai, Tsutomu Imaizumi, Ruruka Suzuki, Marcos Taracena-Gandara, Toshiki Fujimoto, Fuminori Sakurai, Hiroyuki Mizuguchi
Summary: Non-alcoholic liver disease (NAFLD) is caused by excessive fat accumulation in the liver and miR-27b has been found to play a crucial role in NAFLD development by targeting genes involved in lipid metabolism. This study identified MAIP1 as a direct target of miR-27b and showed that overexpression of MAIP1 can ameliorate lipid accumulation induced by miR-27b. Additionally, decreased Maip1 expression was observed in mice fed a high-fat diet, suggesting its involvement in fatty liver condition and its potential as a therapeutic target for NAFLD.
COMMUNICATIONS BIOLOGY
(2023)
Article
Immunology
Masashi Tachibana, Nobumasa Watanabe, Yuzo Koda, Yukako Oya, Osamu Kaminuma, Kazufumi Katayama, Zifei Fan, Fuminori Sakurai, Kenji Kawabata, Takachika Hiroi, Hiroyuki Mizuguchi
INTERNATIONAL IMMUNOLOGY
(2020)
Article
Gastroenterology & Hepatology
Ayumi Kiso, Yukiko Toba, Susumu Tsutsumi, Sayaka Deguchi, Keisuke Igai, Saki Koshino, Yasuhito Tanaka, Kazuo Takayama, Hiroyuki Mizuguchi
HEPATOLOGY COMMUNICATIONS
(2020)