Review
Chemistry, Multidisciplinary
Pei Huang, Hongzhang Deng, Changrong Wang, Yongfeng Zhou, Xiaoyuan Chen
Summary: Messenger RNA (mRNA)-based therapy is a powerful, safe, and rapidly scalable therapeutic approach. In this review, therapeutic applications of mRNA are introduced, common types of mRNA cargos and delivery systems are summarized, and strategies to enhance nanotechnology-mediated mRNA delivery efficiency during the cellular trafficking process are highlighted.
ADVANCED MATERIALS
(2023)
Article
Multidisciplinary Sciences
Hanae Sato, Robert H. Singer
Summary: The author developed a single-cell reporter system to investigate cell-to-cell variability of NMD efficiency. The study revealed a wide range of NMD efficiency in different cells, potentially linked to the expression levels of surveillance factors.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Ariko Miyake, Minh Ha Ngo, Shelly Wulandari, Masayuki Shimojima, So Nakagawa, Junna Kawasaki, Kazuo Nishigaki
Summary: Host genetic resistance to viral infection controls the pathogenicity and epidemic dynamics of infectious diseases. Refrex-1 is a restriction factor that counteracts infection by feline leukemia virus subgroup D and domestic cat endogenous retroviruses. It competes for the entry receptor CTR1 and also shows antiviral effects against primate endogenous retroviruses. Additionally, truncated envelope genes found in various mammalian species can block infection by retroviruses. These findings highlight the convergent evolution of antiviral mechanisms acquired from ancient retroviruses.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Virology
Mengbiao Guo, Jianxi Zhu, Zhijie Hu, Qi Wang, Zhou Songyang, Yuanyan Xiong
Summary: We revealed an incomplete mechanistic understanding of virus infection and inflammation in many diseases. We found that infection by various RNA viruses can induce aberrant polyadenylation of replication-dependent histone (RDH) mRNA, resulting in inflammation or cellular senescence. We further investigated the elevation of this polyadenylation-induced inflammation score (pARIS) in various disease conditions, including virus infection, cancer, and cellular senescence. We identified and experimentally verified two regulators of pARIS, ADAR1 and ZKSCAN1, which are upregulated under most infection and inflammation conditions, and uncovered a potential antiviral mechanism underlying various types of virus infections and cancers.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Multidisciplinary Sciences
Huayu Zhu, Jun Li, Yize Li, Zhao Zheng, Hao Guan, Hongtao Wang, Ke Tao, Jiaqi Liu, Yunchuan Wang, Wanfu Zhang, Chao Li, Jie Li, Lintao Jia, Wendong Bai, Dahai Hu
Summary: This study reveals the roles of glucocorticoid in cellular mechanotransduction and a novel lncRNA-dependent GMD mechanism, offering a potential strategy for early intervention in mechanical disorder-associated diseases.
Article
Virology
Marlene Buckmaster, Stephen P. Goff
Summary: Zinc finger antiviral protein (ZAP) is a potent antiviral molecule that inhibits the replication of various viruses. This study identifies Riplet as a cofactor that enhances the antiviral activity of ZAP. Riplet interacts with ZAP through specific domains and its ubiquitin ligase activity is not required for stimulating ZAP-mediated virus inhibition.
JOURNAL OF VIROLOGY
(2022)
Review
Microbiology
Joshua A. Hayward, Gilda Tachedjian
Summary: Bats are known reservoirs of deadly human viruses, but the potential threat of bat retroviruses to humans remains unclear and requires further research. Recent reports of retroviruses circulating in bat populations are based on decades of research, and the global impact of the COVID-19 pandemic highlights the importance of studying viruses hosted by bats.
Article
Medicine, Research & Experimental
Xiaotong Wang, Jing Wang, Xibo Zhao, Han Wu, Jixin Li, Yan Cheng, Qiuyan Guo, Xuejiao Cao, Tian Liang, Liyuan Sun, Guangmei Zhang
Summary: This study reveals the significant role of METTL3-mediated m6A methylation in the ectopic implantation of endometrial stromal cells (ESCs). Decreased METTL3 expression leads to a downregulation of m6A RNA methylation levels in ESCs. Silencing of m6A modifications mediated by METTL3 enhances the viability, proliferation, migration, and invasion capabilities of ESCs, promoting the progression of endometriosis.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Chemistry, Multidisciplinary
Pei Huang, Lingsheng Jiang, Hui Pan, Lingwen Ding, Bo Zhou, Mengyao Zhao, Jianhua Zou, Benhao Li, Meiwei Qi, Hongzhang Deng, Yongfeng Zhou, Xiaoyuan Chen
Summary: Researchers synthesized a new polymer for mRNA delivery, which showed no inflammatory side effects in vivo and successfully delivered mRNA cancer vaccines, resulting in robust anti-tumor cellular immune response.
ADVANCED MATERIALS
(2023)
Article
Cell Biology
Sejeong Shin, Min-Joon Han, Mark P. Jedrychowski, Ziyang Zhang, Kevan M. Shokal, David R. Plas, Noah Dephoure, Sang-Oh Yoon
Summary: Cells change their proteomes according to their environment and needs, and the key regulator of this process is mTOR. Dysregulation of mTOR leads to changes in proteostasis and the progression of diseases, including cancer.
Review
Cell Biology
Scott Berry, Lucas Pelkmans
Summary: The relationship between mRNA transcript abundance and cell size, as well as the regulation of RNA polymerase II activity and abundance, are discussed in this article. Feedback mechanisms that adjust mRNA synthesis rates, nuclear export, and degradation are also identified, allowing cells to compensate for changes in one aspect by adjusting others. Researchers are integrating findings from different fields to understand the mechanisms underlying transcript homeostasis and its connection to other aspects of the cellular phenotype.
TRENDS IN CELL BIOLOGY
(2022)
Review
Food Science & Technology
Shubhra Pande, Sheikh Raisuddin
Summary: Sirtuins (SIRT) are a unique group of enzymes that can remove acyl groups from lysine residues using NAD+ as a co-substrate. The members of the SIRT family have distinct characteristics and biological functions, affecting various metabolic processes in different cellular locations. Understanding the distribution, specific biological roles, and effects of SIRT in human tissues is crucial for identifying molecular mechanisms and finding foods that can beneficially enhance SIRT activity.
CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION
(2022)
Article
Cell Biology
Deyang Yu, Nicole E. Richardson, Cara L. Green, Alexandra B. Spicer, Michaela E. Murphy, Victoria Flores, Cholsoon Jang, Ildiko Kasza, Maria Nikodemova, Matthew H. Wakai, Jay L. Tomasiewicz, Shany E. Yang, Blake R. Miller, Heidi H. Pak, Jacqueline A. Brinkman, Jennifer M. Rojas, William J. Quinn, Eunhae P. Cheng, Elizabeth N. Konon, Lexington R. Haider, Megan Finke, Michelle Sonsalla, Caroline M. Alexander, Joshua D. Rabinowitz, Joseph A. Baur, Kristen C. Malecki, Dudley W. Lamming
Summary: The study found that different branched-chain amino acids (BCAAs) have distinct metabolic effects, with low isoleucine diet improving hepatic insulin sensitivity and energy expenditure. It is suggested that reducing isoleucine may be a new approach to treating and preventing obesity and diabetes.
Article
Medicine, Research & Experimental
Claudia Del Toro Runzer, Shivesh Anand, Carlos Mota, Lorenzo Moroni, Christian Plank, Martijn van Griensven, Elizabeth R. Balmayor
Summary: Nucleic acids have great potential for gene therapy, with plasmid DNA as the first therapeutic nucleic acid and mRNA as a safer and more affordable option. This study investigated the uptake mechanisms and efficiencies of genetic material by cells, focusing on different nucleic acids, delivery vectors, and human primary cells. The study found that caveolae-mediated uptake was the main route for gene delivery, pDNA had higher expression levels in fast-dividing fibroblasts, cmRNA was responsible for high protein production in slow-dividing osteoblasts, and in mesenchymal stem cells, the combination of vector and nucleic acid was more relevant. Protein expression was higher when cells were seeded on 3D scaffolds.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2023)
Article
Chemistry, Multidisciplinary
Aditya Vasan, Jeremy Orosco, Uri Magaram, Marc Duque, Connor Weiss, Yusuf Tufail, Sreekanth H. Chalasani, James Friend
Summary: The study utilized high-speed digital holographic microscopy to visualize cellular membrane dynamics under ultrasound stimulation and found that both neuronal and fibroblast membranes deflect about 150 nm. A biomechanical model predicting changes in membrane voltage after ultrasound exposure was developed and validated using whole-cell patch clamp electrophysiology. The results demonstrate that ultrasound stimulation directly induces defects in neuronal membranes, leading to changes in membrane voltage.
Article
Oncology
Anna Lieske, Eric Agyeman-Duah, Anton Selich, Nicole Doerpmund, Steven R. Talbot, Axel Schambach, Tobias Maetzig
Summary: Relapse in AML is a major challenge, partly due to the heterogeneity of leukemic stem cells (LSCs). This study shows that LSC potential in a murine AML model is present in three immunophenotypes: Lin(-)cKit(+) progenitor cells, Gr1(+)CD11b(+)cKit(+) myeloid cells, and lymphoid cells. Unexpectedly, a fraction of Lin(-) LSCs failed to regenerate Lym(+) LSCs and had reduced leukemogenic potential. However, Lin(-) LSCs capable of producing Lym(+) LSCs and Lym(+) LSCs triggered aggressive disease development, suggesting their high relapse-driving potential.
Article
Multidisciplinary Sciences
Dejan Mesner, Ann-Kathrin Reuschl, Matthew V. X. Whelan, Taylor Bronzovich, Tafhima Haider, Lucy G. Thorne, Roberta Ragazzini, Paola Bonfanti, Greg J. Towers, Clare Jolly
Summary: The spike protein of SARS-CoV-2 requires proteolytic processing for viral entry. Guanylate-binding proteins (GBP) 2 and 5, interferon-inducible restriction factors, inhibit the infectivity of early-lineage isolates but not the VOCs Alpha and Delta. However, the Omicron variant is unique as it is sensitive to both GBP2/5 and IFITM1, 2, and 3.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Chemistry, Multidisciplinary
Wei-Ju Chen, Wei-Kai Huang, Sarshan R. Pather, Wei-Fang Chang, Li-Ying Sung, Han-Chung Wu, Mei-Ying Liao, Chi-Chiu Lee, Hsuan-Hui Wu, Chung-Yi Wu, Kuo-Shiang Liao, Chun-Yu Lin, Shang-Chih Yang, Hsuan Lin, Pei-Lun Lai, Chi-Hou Ng, Chun-Mei Hu, I-Chih Chen, Chi-Hsuan Chuang, Chien-Ying Lai, Po-Yu Lin, Yueh-Chang Lee, Scott C. Schuyler, Axel Schambach, Frank Leigh Lu, Jean Lu
Summary: This study identifies a membrane protein, PODXL, as a critical regulator of pluripotency in stem cells. It is found that PODXL plays a role in regulating cholesterol levels, which in turn affects the function and characteristics of pluripotent stem cells. Additionally, PODXL is involved in modulating actin network, SREBP transcription factors, and lipid raft dynamics.
Article
Oncology
Robert Polten, Ivana Kutle, Jens Hachenberg, Ruediger Klapdor, Michael Morgan, Axel Schambach
Summary: Current treatments for cervical cancer include surgery, radiation, and chemotherapy, but complete cancer removal is not always possible and some cancer cells may be resistant to treatment. The use of immunotherapies, such as monoclonal antibodies and genetically modified immune cells, shows promise in improving patient survival.
Article
Biochemistry & Molecular Biology
Christian Soehngen, David J. Thomas, Margaretha A. Skowron, Felix Bremmer, Markus Eckstein, Anja Stefanski, Marc D. Driessen, Gamal A. Wakileh, Kai Stuehler, Peter Altevogt, Dan Theodorescu, Ruediger Klapdor, Axel Schambach, Daniel Nettersheim
Summary: This study aimed to understand the molecular function of CD24 in vitro and evaluate the cytotoxic capacity of NK cell CAR against CD24 in urological tumor cells. The results showed that CD24 interacts with proteins involved in cell adhesion, ATP binding, phosphoprotein binding, and post-translational modifications. Treatment with NK-CD24-CAR cells significantly decreased cell viability and induced apoptosis specifically in CD24(+) tumor cells. This study provides a promising novel target for immune therapeutic approaches against urological malignancies.
Article
Hematology
Yang Liu, Ludwig Schmiderer, Martin Hjort, Stefan Lang, Tyra Bremborg, Anna Rydstroem, Axel Schambach, Jonas Larsson, Stefan Karlsson
Summary: This study generated a traceable RPS19-deficient cell model using CRISPR-Cas9 and homology-directed repair, and developed a gentle nanostraw delivery platform to edit the RPS19 gene in primary human cord blood derived CD34+ hematopoietic stem and progenitor cells. The edited cells showed impaired erythroid differentiation phenotype and activated cell cycle-related signaling pathways. This study demonstrates the potential of nanostraws as a gentle option for gene editing in primary hematopoietic stem and progenitor cells.
Letter
Biochemistry & Molecular Biology
Thomas Fox, Juan Bueren, Fabio Candotti, Alain Fischer, Alessandro Aiuti, Arjan Lankester, Michael AGORA Initiative, Michael Albert, Maria Ester Bernardo, Marina Cavazzana, Stephan Ehl, Benedicte Neven, Johan Prevot, Axel Schambach, Julian Sevilla, Adrian Thrasher, Rob Wynn, Claire Booth
Article
Medicine, General & Internal
Robert Chiesa, Christos Georgiadis, Farhatullah Syed, Hong Zhan, Annie Etuk, Soragia Athina Gkazi, Roland Preece, Giorgio Ottaviano, Toni Braybrook, Jan Chu, Agnieszka Kubat, Stuart Adams, Rebecca Thomas, Kimberly Gilmour, David O'Connor, Ajay Vora, Waseem Qasim
Summary: Base editing technique has been used to inactivate genes and treat relapsed childhood T-cell leukemia with promising results.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Medicine, Research & Experimental
Amr H. Saleh, Michael Rothe, Dwayne L. Barber, William M. Mckillop, Graeme Fraser, Chantal F. Morel, Axel Schambach, Christiane Auray-Blais, Michael L. West, Aneal Khan, Daniel H. Fowler, Anthony C. Rupar, Ronan Foley, Jeffrey A. Medin, Armand Keating
Summary: We conducted a DNA insertion site analysis of peripheral blood samples from five male patients with Fabry disease to evaluate the risks of clonal dominance and leukemogenesis. Our study showed a polyclonal integration site spectrum in the patients, with no evidence of a dominant clone. Although vector integrations near proto-oncogenes were identified, they had low percentages of contributions and did not persist over time. Overall, lentivirus-mediated gene therapy for Fabry disease was not associated with the risk of leukemogenic transformation.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2023)
Article
Oncology
Ivana Kutle, Robert Polten, Jens Hachenberg, Ruediger Klapdor, Michael Morgan, Axel Schambach
Summary: Appropriate testing models are crucial for finding effective personalized treatments for different cancers, including advanced cervical cancer. This review provides a comprehensive overview of the currently available 3D models of cervical cancer and their significance in pre-clinical and clinical studies. The review emphasizes the potential of 3D tumor models, such as spheroids and patient-derived organoids, in evaluating novel therapies, especially immunotherapies targeting tumor cells and modulating the tumor microenvironment.
Article
Oncology
Juliette Nowak, Marco Bentele, Ivana Kutle, Katharina Zimmermann, Jonathan Lukas Luehmann, Doris Steinemann, Stephan Kloess, Ulrike Koehl, Willi Rossberg, Amed Ahmed, Dirk Schaudien, Lavinia Neubert, Jan-Christopher Kamp, Mark P. Kuehnel, Athanasia Warnecke, Axel Schambach, Michael Morgan
Summary: Despite poor prognosis and survival rates for head and neck squamous cell carcinomas (HNSCC), immunotherapy using CAR-NK cells targeting HER1/EGFR shows promise for HNSCC treatment. However, targeting HER1 alone is not sufficient to eliminate potential cancer stem cells. It is necessary to target multiple tumor-associated antigens to reduce high relapse rates in HNSCC.
Article
Biotechnology & Applied Microbiology
Bianca Altvater, Sareetha Kailayangiri, Christian Spurny, Maike Fluegge, Jutta Meltzer, Lea Greune, Katja Urban, Christian Schwoeppe, Caroline Brand, Christoph Schliemann, Heike Hintelmann, Saliha Harrach, Wolfgang Hartmann, Hinrich Abken, Johannes Kuehle, Axel Schambach, Dennis Goerlich, Wolfgang E. Berdel, Claudia Rossig
Summary: To improve the effectiveness of CAR-engineered T cells in solid cancers, we developed a novel cell-based combination strategy involving an additional therapeutic mode of action. In this strategy, CAR T cells act as micropharmacies that produce a targeted coagulation protein called tTF-NGR, which induces blood clotting and hypoxia when it localizes to the vascular endothelial cells in tumor tissues. This approach aims to create locoregional tumor vascular infarction and combined immune-mediated and hypoxic tumor cell death.
CANCER GENE THERAPY
(2023)
Article
Medicine, Research & Experimental
Antonella L. Bastone, Violetta Dziadek, Philipp John-Neek, Friederike Mansel, Jenni Fleischauer, Eric Agyeman-Duah, Dirk Schaudien, Oliver Dittrich-Breiholz, Adrian Schwarzer, Axel Schambach, Michael Rothe
Summary: Safety assessment in retroviral vector-mediated gene therapy is challenging due to the risk of insertional mutagenesis. The authors developed two assays, IVIM and SAGA, to predict genotoxicity of integrating vectors. However, both assays have a myeloid bias, so the authors investigated lymphoid mutants and identified unique gene expression changes. The highly sensitive molecular readout based on gene expression will contribute to preclinical prediction of retroviral genotoxicity.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2023)
Article
Cell Biology
Jenni Fleischauer, Antonella Lucia Bastone, Anton Selich, Philipp John-Neek, Luisa Weisskoeppel, Dirk Schaudien, Axel Schambach, Michael Rothe
Summary: Researchers developed cell culture conditions to maintain the stemness of murine hematopoietic stem and progenitor cells (HSPCs) and prevent differentiation. They used A83-01, pomalidomide, and UM171 (APU) to attenuate differentiation and preserve the stemness of HSPCs. Expanded HSPCs showed functional characteristics and could be used for retroviral vector testing and genotoxicity studies.
Meeting Abstract
Oncology
Bianca Altvater, Sareetha Kailayangiri, Christian Spurny, Maike Flugge, Jutta Meltzer, Lea Greune, Christian Schwoppe, Caroline Brand, Christoph Schliemann, Wolfgang Hartmann, Hinrich Abken, Axel Schambach, Nicole Farwick, Wolfgang E. Berdel, Claudia Rossig