Article
Multidisciplinary Sciences
Xiangjun He, Zhenjie Zhang, Junyi Xue, Yaofeng Wang, Siqi Zhang, Junkang Wei, Chenzi Zhang, Jue Wang, Brian Anugerah Urip, Chun Christopher Ngan, Junjiang Sun, Yuefeng Li, Zhiqian Lu, Hui Zhao, Duanqing Pei, Chi-Kong Li, Bo Feng
Summary: The authors developed an AAV-CRISPR mediated somatic knock-in method and applied it to treat hemophilia B. The results showed liver-specificity of the knock-in and low serum antibody production, making it a promising approach for long-term hemostasis restoration.
NATURE COMMUNICATIONS
(2022)
Article
Biochemical Research Methods
James Zengel, Yu Xin Wang, Jai Woong Seo, Ke Ning, James. N. N. Hamilton, Bo Wu, Marina Raie, Colin Holbrook, Shiqi Su, Derek. R. R. Clements, Sirika Pillay, Andreas. S. S. Puschnik, Monte. M. M. Winslow, Juliana Idoyaga, Claude. M. M. Nagamine, Yang Sun, Vinit. B. B. Mahajan, Katherine. W. W. Ferrara, Helen. M. M. Blau, Jan. E. E. Carette
Summary: SELECTIV is an efficient method that enables tissue-specific transgene expression in mice through AAV receptor overexpression. It significantly improves the efficiency and specificity of AAV transduction in various cell types by coupling AAV vectors with Cre-inducible overexpression of the multi-serotype AAV receptor, AAVR. The enhanced efficacy and exquisite specificity of SELECTIV have broad applications in the development of new mouse model systems and gene delivery in vivo using AAV.
Article
Gastroenterology & Hepatology
Greta Acerbi, Ilaria Montali, Gennaro Domenico Ferrigno, Valeria Barili, Simona Schivazappa, Arianna Alfieri, Diletta Laccabue, Alessandro Loglio, Marta Borghi, Marco Massari, Marzia Rossi, Andrea Vecchi, Amalia Penna, Carolina Boni, Gabriele Missale, Pietro Lampertico, Daniele Del Rio, Carlo Ferrari, Paola Fisicaro
Summary: In chronic HBV infection, virus-specific CD8 T cells show impaired autophagic flux, while bioactive compounds such as resveratrol and oleuropein can improve mitochondrial and proteostasis functions in T cells. The combination of polyphenols with antioxidants represents a promising strategy for immune reconstitution in chronic HBV infection.
JOURNAL OF HEPATOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Shinnosuke Tsuji, Calvin J. Stephens, Giulia Bortolussi, Feijie Zhang, Gabriele Baj, Hagoon Jang, Gustavo de Alencastro, Andres F. Muro, Katja Pekrun, Mark A. Kay
Summary: The use of ribonucleotide reductase inhibitors can substantially enhance the efficiency of adeno-associated virus-mediated homologous recombination-based gene therapy. These findings suggest that clinically approved inhibitors, such as fludarabine, can be used to potentiate gene editing therapies.
NATURE BIOTECHNOLOGY
(2022)
Review
Immunology
Hildegund C. J. Ertl
Summary: Adeno-associated virus (AAV)-mediated gene transfer has shown benefits in treating patients with inherited diseases like hemophilia B, but challenges remain due to potential rejection of AAV-transduced cells. Immunosuppression may prevent rejection in some patients. CD8(+) T cells induced by AAV infections may recognize AAV vector's capsids and eliminate cells expressing degraded capsid antigens, or AAV vectors themselves may induce de novo T cell responses, particularly at high doses. This chapter discusses strategies to prevent activation of CD8(+) T cell responses to AAV infections and gene transfer.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Pharmacology & Pharmacy
Guangna Liu, Motao Zhu, Xiao Zhao, Guangjun Nie
Summary: Vaccination has become an effective method to stimulate immunity for disease prevention and treatment, but a tailored efficient delivery system for specific antigens is still urgently needed, especially for vaccines targeting CD8(+) T cells-mediated cellular immunity. Nanotechnology plays a crucial role in enhancing antigen stability and immunogenicity, as well as facilitating APCs-targeted delivery and increased cross-presentation for effective immune protection and clearance.
ADVANCED DRUG DELIVERY REVIEWS
(2021)
Article
Biochemistry & Molecular Biology
Sam Hana, Michael Peterson, Helen McLaughlin, Eric Marshall, Attila J. Fabian, Olivia McKissick, Kathryn Koszka, Galina Marsh, Michael Craft, Shanqin Xu, Alexander Sorets, Tess Torregrosa, Chao Sun, Chris E. Henderson, Shih-Ching Lo
Summary: CRISPR-Cas systems have been utilized as a powerful tool for generating genetic models to study the central nervous system, achieving successful targeted gene disruption in neurons. By optimizing key parameters and RNA design, high efficiency gene knockout rates have been achieved, contributing valuable insights for both fundamental and preclinical research.
Article
Multidisciplinary Sciences
Megha Subramanian, James McIninch, Ivan Zlatev, Mark K. Schlegel, Charalambos Kaittanis, Tuyen Nguyen, Saket Agarwal, Timothy Racie, Martha Arbaiza Alvarado, Kelly Wassarman, Thomas S. Collins, Tyler Chickering, Christopher R. Brown, Karyn Schmidt, Adam B. Castoreno, Svetlana Shulga-Morskaya, Elena Stamenova, Kira Buckowing, Daniel Berman, Joseph D. Barry, Anna Bisbe, Martin A. Maier, Kevin Fitzgerald, Vasant Jadhav
Summary: The authors propose an RNA interference-based switch to control AAV transgene expression. They use RNAi to silence transgene expression and then recover it using REVERSIR oligonucleotides. This approach has the potential for clinical application in gene therapy.
NATURE COMMUNICATIONS
(2023)
Article
Immunology
Marko Sustic, Maja Cokaric Brdovcak, Berislav Lisnic, Jelena Materljan, Vanda Juranic Lisnic, Carmen Rozmanic, Daniela Indenbirken, Lea Hirsl, Dirk H. Busch, Ilija Brizic, Astrid Krmpotic, Stipan Jonjic
Summary: CMV vectors have the potential to induce strong immune responses, with RAE-1 gamma MCMV showing enhanced immunoprotection against bacterial and tumor challenges. The phenotypic and functional characteristics of memory CD8 T cells induced by RAE-1 gamma MCMV were distinct compared to control vectors, with differences in cytokine production and cytotoxic potential. Adoptive transfer of cells primed with RAE-1 gamma MCMV led to efficient rejection of established tumors, highlighting the importance of latent infection and cell numbers in enhancing anti-tumor responses.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Trevor J. Gonzalez, Katherine E. Simon, Leo O. Blondel, Marco M. Fanous, Angela L. Roger, Maribel Santiago Maysonet, Garth W. Devlin, Timothy J. Smith, Daniel K. Oh, L. Patrick Havlik, Ruth M. Castellanos Rivera, Jorge A. Piedrahita, Mai K. ElMallah, Charles A. Gersbach, Aravind Asokan
Summary: Researchers have successfully generated a cross-species compatible AAV (ccAAVs) vector using a viral evolutionary approach, and discovered a highly potent new variant AAV.cc47. AAV.cc47 demonstrated enhanced transduction efficiency compared to AAV serotype 9 in mouse, pig, and non-human primate models, showing great potential for gene therapy. This study focuses on investigating cross-species delivery of AAV and provides new theoretical insights for translating gene therapy into clinical applications.
NATURE COMMUNICATIONS
(2022)
Review
Clinical Neurology
Marika Marino, Matthew G. Holt
Summary: Monoclonal antibodies and their derivatives are powerful therapeutics due to their targeting specificity, but their use in Central Nervous System diseases has been slow due to limited Blood Brain Barrier permeability. However, as CNS diseases become more prevalent, there is a growing need to utilize the therapeutic potential of monoclonal antibodies. Adeno-associated virus-based vectors show promise in delivering antibodies to the CNS and could be used to target CNS proteinopathies.
FRONTIERS IN NEUROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Terence R. Flotte, Oguz Cataltepe, Ajit Puri, Ana Rita Batista, Richard Moser, Diane McKenna-Yasek, Catherine Douthwright, Gwladys Gernoux, Meghan Blackwood, Christian Mueller, Phillip W. L. Tai, Xuntian Jiang, Scot Bateman, Spiro G. Spanakis, Julia Parzych, Allison M. Keeler, Aly Abayazeed, Saurabh Rohatgi, Laura Gibson, Robert Finberg, Bruce A. Barton, Zeynep Vardar, Mohammed Salman Shazeeb, Matthew Gounis, Cynthia J. Tifft, Florian S. Eichler, Robert H. Brown, Douglas R. Martin, Heather L. Gray-Edwards, Miguel Sena-Esteves
Summary: This study presents the results of AAV gene therapy in two patients with infantile TSD. The treatment was well tolerated without vector-related adverse events, and demonstrated an increase and stability of HexA activity in the cerebrospinal fluid. One patient showed disease stabilization, while the other experienced disease progression after treatment.
Article
Immunology
Sophia Giang, David A. Horwitz, Sean Bickerton, Antonio La Cava
Summary: This study introduces a method to produce acellular tolerogenic aAPCs using PLGA nanoparticles, which can induce human T cells to become functional Tregs and modulate systemic autoimmunity. It highlights the potential of using PLGA NPs as a targeted approach to repair IL-2 and/or TGF-beta defects in autoimmune diseases.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Agata Antepowicz, Omar Habib, Freja Kirsebom, Cecilia Johansson, Deborah R. Gill, Stephen C. Hyde
Summary: In this study, gene delivery approaches using recombinant adeno-associated virus and simian immunodeficiency virus vectors were utilized to achieve sustained in vivo production of Palivizumab in a murine model. Pre-treatment with Palivizumab-expressing vectors provided complete protection against RSV-induced weight loss. This approach offers prophylaxis against RSV infection, potentially reducing treatment costs in vulnerable populations.
SCIENTIFIC REPORTS
(2021)
Article
Virology
Nozomi Kuse, Tomohiro Akahoshi, Masafumi Takiguchi
Summary: The study demonstrated that priming with STING ligand 3'3'-cGAMP effectively activated HLA-B*52:01-restricted CD8(+) T cells, which showed strong ability to suppress HIV-1 replication and expressed high levels of cytolytic effector molecules. This suggests that priming with STING ligand of functional CD8(+) T cells specific for protective epitopes could be beneficial in an HIV-1 cure therapy.
JOURNAL OF VIROLOGY
(2021)
Article
Oncology
Toshiyuki Seki, Jianyun Liu, Randy R. Brutkiewicz, Moriya Tsuji
ANTICANCER RESEARCH
(2019)
Article
Microbiology
Huapeng Feng, Noriko Nakajima, Li Wu, Makoto Yamashita, Tiago J. S. Lopes, Moriya Tsuji, Hideki Hasegawa, Tokiko Watanabe, Yoshihiro Kawaoka
FRONTIERS IN MICROBIOLOGY
(2019)
Article
Immunology
Jordana G. A. Coelho-dos-Reis, Ryota Funakoshi, Jing Huang, Felipe Valenca Pereira, Sho Iketani, Moriya Tsuji
JOURNAL OF INFECTIOUS DISEASES
(2020)
Article
Biochemistry & Molecular Biology
Kriti Kalpana, Shen Yap, Revathi Iyengar, Moriya Tsuji, Akira Kawamura
CHEMICAL BIOLOGY & DRUG DESIGN
(2020)
Article
Chemistry, Multidisciplinary
Nina Hartrampf, Toshiyuki Seki, Andreas Baumann, Philip Watson, Nynke A. Veprek, Belinda E. Hetzler, Anja Hoffmann-Roder, Moriya Tsuji, Dirk Trauner
CHEMISTRY-A EUROPEAN JOURNAL
(2020)
Editorial Material
Immunology
Moriya Tsuji, Ramesh Akkina
FRONTIERS IN IMMUNOLOGY
(2020)
Article
Immunology
Vinayaka Kotraiah, Timothy W. Phares, Cecille D. Browne, James Pannucci, Marc Mansour, Amy R. Noe, Kenneth D. Tucker, Jayne M. Christen, Charles Reed, Alecia MacKay, Genevieve M. Weir, Rajkannan Rajagopalan, Marianne M. Stanford, Chun-Shiang Chung, Alfred Ayala, Jing Huang, Moriya Tsuji, Gabriel M. Gutierrez
FRONTIERS IN IMMUNOLOGY
(2020)
Article
Immunology
Alemu Tekewe Mogus, Lihong Liu, Manxue Jia, Diane T. Ajayi, Kai Xu, Rui Kong, Jing Huang, Jian Yu, Peter D. Kwong, John R. Mascola, David D. Ho, Moriya Tsuji, Bryce Chackerian
Article
Oncology
Xuedan He, Shiqi Zhou, Melissa Dolan, Yuhao Shi, Jianxin Wang, Breandan Quinn, Dushyant Jahagirdar, Wei-Chiao Huang, Moriya Tsuji, Roberto Pili, Fumito Ito, Joaquin Ortega, Scott Abrams, John M. L. Ebos, Jonathan F. Lovell
Summary: The study successfully predicted and screened MHC-I restricted neoepitopes in a murine renal adenocarcinoma model, converting them into immunogenic nanoparticles which induced antitumor responses. One candidate neoepitope, Nesprin-2 L4492R (Nes2LR), not only induced functional responses within 20-plex or 60-plex particles, but also prevented tumor growth.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Biochemistry & Molecular Biology
Felicia N. N. Watson, Caroline J. Duncombe, Anya C. C. Kalata, Ethan Conrad, Sumana Chakravarty, B. Kim Lee Sim, Stephen L. L. Hoffman, Moriya J. Tsuji, Melanie J. Shears, Sean C. C. Murphy
Summary: 7DW8-5 is a potent glycolipid adjuvant that improves malaria vaccine efficacy in mice by inducing IFN-gamma and increasing protective CD8(+) T cell responses. However, there are significant differential sex-specific responses to 7DW8-5, with male mice showing lower cytokine production and reduced vaccine efficacy compared to females. These findings highlight the importance of including both female and male sexes in experimental adjuvant studies.
Article
Biochemistry & Molecular Biology
Kriti Kalpana, Shen Yap, Moriya Tsuji, Akira Kawamura
Summary: This study reveals that Withaferin A can selectively attenuate the pro-inflammatory signaling triggered by endotoxin without impairing other immunological pathways, providing a new conceptual framework to understand the safe immune-boosting effect of Withania somnifera and possibly other medicinal plants. The findings also open new opportunities for the development of safe immunotherapeutic agents, such as vaccine adjuvants.
Article
Biochemistry & Molecular Biology
Thaiza Aline Pereira-Santos, Anderson Santos da Rocha, Agata Lopes-Ribeiro, Laura Cardoso Correa-Dias, Patricia Melo-Oliveira, Erik Vinicius de Sousa Reis, Flavio Guimaraes da Fonseca, Edel Figueiredo Barbosa-Stancioli, Moriya Tsuji, Jordana Grazziela Alves Coelho-dos-Reis
Summary: This study aimed to identify immunodominant regions of HTLV-1 Tax using peptide microarray analysis. Results showed dose-dependent reactivity of HLA-A*02:01 in all regions, with specific hotspots. In silico analysis revealed IFN-gamma-inducing peptides in the N-terminal portion and IL-4 inducers in the C-terminal portion. This research provides insight for designing immunomodulatory strategies for HTLV-1 chronic diseases.
Article
Multidisciplinary Sciences
Moriya Tsuji, Manoj S. S. Nair, Kazuya Masuda, Candace Castagna, Zhenlu Chong, Tamarand L. L. Darling, Kuljeet Seehra, Youngmin Hwang, agata Lopes Ribeiro, Geovane Marques Ferreira, Laura Corredor, Jordana Grazziela Alves Coelho-dos-Reis, Yukiko Tsuji, Munemasa Mori, Adrianus C. M. Boon, Michael S. Diamond, Yaoxing Huang, David D. Ho
Summary: A glycolipid called 7DW8-5 has been found to stimulate NKT cells to release cytokines and chemokines, enabling rapid control of viral infections. Intranasal administration of 7DW8-5 effectively blocked infections by various variants of SARS-CoV-2, respiratory syncytial virus, and influenza virus. This glycolipid could be a useful tool in preventing virus spread and responding to future pandemics.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Yang Xu, Tammy Ferguson, Kazuya Masuda, Mohammad Adnan Siddiqui, Kelsi Poole Smith, Olivia Vest, Brad Brooks, Ziyou Zhou, Judy Obliosca, Xiang-Peng Kong, Xunqing Jiang, Masahiro Yamashita, Tsuji Moriya, Christopher Tison
Summary: Luna Labs is developing a short carbon nanotube-based delivery platform called NanoVac, which can efficiently co-deliver mRNA and HIV-1 glycoproteins to the immune system with negligible toxicity. NanoVac stabilized the loaded mRNA and reduced the cold chain burden for vaccine deployment.
Letter
Immunology
Kyle C. McKenna, Moriya Tsuji
JOURNAL OF IMMUNOLOGY
(2018)