Article
Biotechnology & Applied Microbiology
Yide Huang, Ting Lin, Lingfang Lu, Fan Cai, Jie Lin, Yu'e Jiang, Yao Lin
Summary: A new codon pair optimization algorithm was introduced in this study, showing that codon optimization based on codon pair bias is more effective in enhancing protein expression levels in Pichia pastoris.
MICROBIAL CELL FACTORIES
(2021)
Article
Biochemistry & Molecular Biology
A. Gutierrez-Ortega, D. A. Moreno, S. A. Ferrari, H. Espinosa-Andrews, E. P. Ortiz, F. Milian-Suazo, A. H. Alvarez
Summary: Translation engineering and bioinformatics have accelerated the optimization of gene sequences in E. coli to produce multi-epitope proteins. The fusion protein was expressed successfully and showed antigenic properties for diagnostic purposes, stimulating specific T-cell responses in bovine TB suspects.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Biology
Matthew J. Ranaghan, Jeffrey J. Li, Dylan M. Laprise, Colin W. Garvie
Summary: Custom genes have become popular in recombinant biology due to the decreasing cost of DNA synthesis in the past 20 years. However, there is little consensus among codon-optimization algorithms on what constitutes an optimized CDS, leading to variability in recombinant yields. A study suggests that median codon frequency may be a better predictor of soluble yields than the commonly used CAI metric.
Article
Immunology
Pankaj Gurjar, Noushad Karuvantevida, Igor Vladimirovich Rzhepakovsky, Azmat Ali Khan, Rekha Khandia
Summary: The study identified specific molecular patterns in the structural genes of the SARS-CoV-2 delta variant, including an abundance of T nucleotides, underrepresentation of certain dinucleotides, and specific codon usage preferences. The virus uses these patterns to reduce translation rate and facilitate correct protein folding. This information can be utilized to design an attenuated vaccine candidate against the SARS-CoV-2 delta variant.
Article
Biotechnology & Applied Microbiology
Xavier Hernandez-Alias, Hannah Benisty, Leandro G. Radusky, Luis Serrano, Martin H. Schaefer
Summary: The study reveals tissue-specific codon preferences and their impact on protein synthesis. A machine learning model identifies clusters of tissues with different codon usage patterns. The developed algorithm, CUSTOM, optimizes protein production by suggesting synonymous codon design. This research has implications in gene design and biotechnological applications.
Article
Biochemistry & Molecular Biology
Saadet Kalakenger, Seyda Yildiz Arslan, Fatma Turhan, Melek Acar, Kubra Solak, Ahmet Mavi, Yagmur Unver
Summary: This study aimed to improve the transfection efficiency of MCF-10A cells by delivering recombinant DNA using magnetic nanoparticles (MNPs) and a magnet. Positively modified silica-coated iron oxide MNPs (MSNP-NH2) were produced and characterized. The recombinant DNA (rDNA) was obtained by integrating codon-optimized azurin and validated in Escherichia coli cells. The electrostatically conjugated rDNA on MSNP-NH2 with an enhancer polyethyleneimine (PEI) was applied to the cell, resulting in successful transfer of the azurin gene.
MOLECULAR BIOTECHNOLOGY
(2023)
Article
Biology
Julie D. Thompson, Raymond Ripp, Claudine Mayer, Olivier Poch, Christian J. Michel
Summary: The X circular code is a set of 20 trinucleotides identified in the majority of organisms' protein-coding genes, functioning as an error-correcting code. Research suggests that X motifs, specific codon series of the X circular code, may play a role in maintaining reading frames in genes and potentially influencing gene expression regulation. Additionally, experimental evidence indicates a correlation between X motifs density, translation efficiency, and mRNA stability, suggesting their involvement in genetic signal processing.
Article
Multidisciplinary Sciences
Jiajing Sheng, Xuan She, Xiaoyu Liu, Jia Wang, Zhongli Hu
Summary: This study systematically analyzed the codon usage patterns of Miscanthus plants and related species, revealing a preference for A/T bases and A/T-ending codons in the chloroplast genomes. The results suggested that the codon usage patterns are mainly influenced by natural selection, and Arabidopsis thaliana, Populus trichocarpa, and Saccharomyces cerevisiae could be considered as preferential exogenous expression receptors.
Article
Biotechnology & Applied Microbiology
Kunshan Liu, Yaqi Ouyang, Ru Lin, Chenyu Ge, Mian Zhou
Summary: Codon usage bias plays an important role in regulating gene expression levels, mRNA and protein stabilities in P. pastoris. Extreme codon optimization in genes with strong negative correlation between codon usage bias and protein structural disorder tendency may not be favored, and may affect protein structural conformation more severely in structural disordered proteins.
JOURNAL OF BIOTECHNOLOGY
(2022)
Editorial Material
Multidisciplinary Sciences
Nathaniel Sharp
Summary: Systematic editing of yeast genes to produce mutations reveals that the fitness of yeast is similarly affected by the mutations, regardless of whether the protein sequences encoded by the mutated genes change.
Article
Chemistry, Multidisciplinary
Yuxin Yang, Haijun Ning, Tianping Xia, Jianjun Du, Wen Sun, Jiangli Fan, Xiaojun Peng
Summary: An amphiphilic siRNA-photosensitizer conjugate (siPLK1-NB) that can self-assemble into nanoparticles has been developed for efficient siRNA delivery and lysosomal escape. These nanoparticles exhibit rapid cell endocytosis and outstanding tumor-targeting property. The reactive oxygen species generated after photoactivation can disrupt the lysosome membrane structure and facilitate siRNA escape, leading to effective inhibition of tumor cell growth.
ADVANCED MATERIALS
(2023)
Article
Biochemistry & Molecular Biology
Michael Shaferman, Melis Gencel, Noga Alon, Khawla Alasad, Barak Rotblat, Adrian W. R. Serohijos, Lital Alfonta, Shimon Bershtein
Summary: The variability in codon bias between bacterial genomes can interfere with horizontal gene transfer, which drives bacterial adaptation. This study designed an experimental system to investigate the constraints imposed by codon bias on the integration of transferred genes. It was found that mRNA folding stability plays a dominant role in fitness contribution when horizontal gene transfer leads to overstabilization of the 5'-end mRNA.
MOLECULAR BIOLOGY AND EVOLUTION
(2023)
Article
Oncology
Xisha Chen, Kuansong Wang, Shilong Jiang, Hongyin Sun, Xuanling Che, Minghui Zhang, Jiaying He, Ying Wen, Mengting Liao, Xiangling Li, Xiaoming Zhou, Jianxun Song, Xingcong Ren, Wenjun Yi, Jinming Yang, Xiang Chen, Mingzhu Yin, Yan Cheng
Summary: Our study reveals that eEF2K is correlated with therapeutic response and prognosis in melanoma patients treated with anti-PD-1 therapy. We also show that eEF2K plays a vital role in regulating the tumor immune microenvironment by controlling PD-L1 expression. In addition, combining eEF2K inhibition with ICB therapy may provide a potential combination therapeutic strategy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Neurosciences
Rekha Khandia, Mohd. Saeed, Ahmed M. Alharbi, Ghulam Md. Ashraf, Nigel H. Greig, Mohammad Amjad Kamal
Summary: Codon usage analysis is important for molecular characterization and understanding gene evolution. This study investigated the association between gene length and various parameters related to codon usage. The findings showed a significant correlation between gene length and codon bias in neurodegeneration-associated genes. However, this association varied depending on the size of gene segments. The study also found that gene length was associated with nucleotide disproportion and codon choices. This analysis provides insights into gene expression and potential interventions in defective gene functioning in clinical settings.
FRONTIERS IN NEUROSCIENCE
(2022)
Review
Food Science & Technology
Lucia Citores, Rosario Iglesias, Jose M. Ferreras
Summary: Ribosome-inactivating proteins (RIPs) are enzymes from plants that inhibit protein synthesis and have been studied for decades for their antiviral properties. With the challenges posed by new viruses and difficult-to-treat viral infections, interest in RIPs is increasing. Moreover, the need to control crop diseases without using harmful phytosanitary products has led to RIPs being explored as promising tools for developing virus-resistant transgenic plants.
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
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