Review
Microbiology
Mary Garvey
Summary: This passage introduces the importance of biologics in medical research and the definition of biologics. It also describes in detail the application and advantages of eukaryotic expression systems in the production of biologics.
Article
Biotechnology & Applied Microbiology
Shiva Izadi, Ulrike Vavra, Stanislav Melnik, Clemens Gruenwald-Gruber, Esther Foederl-Hoebenreich, Markus Sack, Kurt Zatloukal, Josef Gloessl, Eva Stoeger, Lukas Mach, Alexandra Castilho, Richard Strasser
Summary: Researchers engineered ACE2-Fc by modifying its glycan structure and obtained an ACE2-Fc variant with enhanced virus-neutralization activity, which shows promise as a potential drug candidate against coronavirus infections.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
Review
Biotechnology & Applied Microbiology
Richard Strasser
Summary: Protein glycosylation has a significant impact on biological processes. The type of glycan on a recombinant glycoprotein depends on protein features and cell glycosylation capabilities. Glycoengineering approaches are used to achieve specific glycan modifications, allowing for structure-function studies and optimization of therapeutic proteins.
BIOTECHNOLOGY ADVANCES
(2023)
Review
Biotechnology & Applied Microbiology
Le Gao, Yi Jiang, Kai Hong, Xiaoyi Chen, Xin Wu
Summary: Protein glycosylation is a complex posttranslational modification process. Cellulases from fungi contain N-glycosylation and O-glycosylation. This study discusses the potential roles of glycosylation on cellulase characteristics and function. Glycoengineering can be used to control cellulase glycosylation by modifying the 3D structure through specially distributed glycans. Understanding the regulatory role of cellulase glycosylation will enable synthetic biology approaches for commercial cellulase development.
CRITICAL REVIEWS IN BIOTECHNOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Sandra Behren, Manuel Schorlemer, Gudula Schmidt, Klaus Aktories, Ulrika Westerlind
Summary: In the last decade, protein mucin-type O-glycosylation and O-GlcNAcylation have been found to modify Tyr residues in addition to Thr and Ser residues. These modifications, known as GlcNAc-O-Tyr and GalNAc-O-Tyr, have been identified on various proteins and have been implicated in bacterial virulence. However, their biological functions and biosynthesis are not well understood due to a lack of detection tools. In this study, antibodies were raised to selectively detect proteins carrying these modifications, and synthetic O-glycopeptides were prepared for microarray analysis. The antibodies showed specific detection of GlcNAc- and GalNAc-O-Tyr modified proteins, providing a valuable tool for further research.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Immunology
Somanath Kallolimath, Roman Palt, Esther Foederl-Hoebenreich, Lin Sun, Qiang Chen, Florian Pruckner, Lukas Eidenberger, Richard Strasser, Kurt Zatloukal, Herta Steinkellner
Summary: This study successfully produced pentameric IgM antibodies in glycoengineered plants that carry a highly reproducible human-type N-glycosylation profile. The pentameric IgMs showed increased antigen binding and virus neutralization potency, up to 390-fold, compared to the parental IgG1.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Baoquan Chen, Wenqiang Liu, Yaohao Li, Bo Ma, Shiying Shang, Zhongping Tan
Summary: Therapeutic proteins are increasingly valued for their unique advantages in the treatment of various diseases, but their intrinsic limitations often restrict their wider applications. Glycosylation, as a crucial post-translational modification, has positive effects on protein properties. Glycoengineering, involving changing glycosylation patterns, is expected to be an effective means of improving the performance of therapeutic proteins.
Article
Chemistry, Analytical
Zhen Zheng, Min Ma, Yifei Jia, Yusi Cui, Rui Zhao, Shuangshuang Li, Cody Wenthur, Lingjun Li, Gongyu Li
Summary: Conjugate vaccines are a promising strategy for immunotherapeutic intervention in substance use disorder. These vaccines utilize a hapten similar to the target drug, which is conjugated to an immunogenic carrier protein. The antibodies produced provide long-lasting protection against drug overdose by sequestering the drug in the periphery and preventing it from crossing the blood-brain barrier. However, these antibodies exhibit structural heterogeneity, and the relationship between their variations and stability remains unclear. This study presents a rapid mass-spectrometry-based workflow that can assess the conformational heterogeneity and stability of crude antibodies in response to conjugate vaccines.
ANALYTICAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Esteban Cruz, Vicki Sifniotis, Zeynep Sumer-Bayraktar, Mouhamad Reslan, Lorna Wilkinson-White, Stuart Cordwell, Veysel Kayser
Summary: Protein aggregation is a common issue in the production and clinical use of therapeutic monoclonal antibodies. By inserting N-glycosylation sequons in the Fab region, the physical stability of the protein can be increased, preventing self-association of antibody monomers and protein aggregation. Further studies show that additional glycosylation can enhance physical stability, shedding light on potential applications for the development of better antibodies.
Article
Chemistry, Multidisciplinary
Maximilian Brueckner, Johanna Simon, Katharina Landfester, Volker Mailaender
Summary: Antibody-modified drug delivery systems in the nano-range show potential in overcoming current challenges for disease treatment due to their high specificity, but no clinically approved antibody-bound nanocarrier exists. Different conjugation strategies influence the spatial orientation of antibodies on the nanocarriers' surface, impacting the success of antibody functionalized drug delivery systems. In this study, two conjugation strategies were compared, showing that both thiol-maleimide coupling and copper-free click chemistry can induce dendritic cell uptake, with orientation of antibodies affecting the targeting efficiency.
Article
Biochemical Research Methods
Tejinder Kaur, Bhupendra Nath Shukla, Vinay Kumar Yadav, Mahesh J. Kulkarni, Alka Rao
Summary: This study compared the glycoprofiles of eight rituximab drug samples licensed for sale in India and found variations in abundance of some glycans within the tested population. The quality range of glycosylation parameters of the tested samples differed significantly from the previously established values for US/EU licensed rituximab. This approach may be useful in defining the true range of glycan variations in licensed versions of therapeutic mAbs.
JOURNAL OF PROTEOMICS
(2021)
Article
Oncology
JongAh Joanne Lee, Nayoung Lee, Young Jun Seo, Ilkoo Kim
Summary: The study aimed to demonstrate the consistent quality profile of the SB5 drug product from 2013 to 2022. Analysis of 93 batches showed that the purity, charge variants, and functional activities of SB5 remained within the defined acceptance criteria, ensuring its safety and efficacy.
Article
Multidisciplinary Sciences
Uri Nimrod Ramirez-Jarquin, Manish Sharma, Wuyue Zhou, Neelam Shahani, Srinivasa Subramaniam
Summary: This study demonstrates that SUMO1 plays a critical role in the pathogenesis of Huntington disease (HD). Deletion of SUMO1 prevents age-dependent motor and neurological impairments, reduces striatal atrophy and inflammatory response in HD mice. SUMO1 deletion affects the levels and distribution of mHtt and promotes autophagic activity. Inhibiting SUMOylation enhances autophagy and reduces mHTT levels in human HD fibroblasts.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Roy A. Ehling, Cedric R. Weber, Derek M. Mason, Simon Friedensohn, Bastian Wagner, Florian Bieberich, Edo Kapetanovic, Rodrigo Vazquez-Lombardi, Raphael B. Di Roberto, Kai-Lin Hong, Camille Wagner, Michele Pataia, Max D. Overath, Daniel J. Sheward, Ben Murrell, Alexander Yermanos, Andreas P. Cuny, Miodrag Savic, Fabian Rudolf, Sai T. Reddy
Summary: This study presents a technology pipeline that combines single-cell antibody repertoire sequencing and mammalian display to investigate the specificity of plasma cells from convalescent COVID-19 patients. The results reveal specific antibodies targeting SARS-CoV-2 antigens, including those with high affinity and broad binding to the receptor binding domain (RBD) of SARS-CoV-2 variants.
Article
Microbiology
Ilaria Varotto-Boccazzi, Alessandro Manenti, Francesca Dapporto, Louise J. Gourlay, Beatrice Bisaglia, Paolo Gabrieli, Federico Forneris, Silvia Faravelli, Valentina Bollati, Diego Rubolini, Gianvincenzo Zuccotti, Emanuele Montomoli, Sara Epis, Claudio Bandi
Summary: Emerging epidemics require rapid development of diagnostic assays, with serological tests taking longer to design. By utilizing Leishmania tarentolae to express SARS-CoV-2 antigens, we were able to successfully apply this for serodiagnosis of Coronavirus infections.
FRONTIERS IN MICROBIOLOGY
(2021)
Review
Cardiac & Cardiovascular Systems
Soo Ghee Yeoh, Jia Siang Sum, Jing Yi Lai, W. Y. Haniff Isa, Theam Soon Lim
Summary: Cardiovascular disease is a leading cause of death globally, with the lipid hypothesis proposing a linkage between plasma cholesterol levels and the risk of developing CVD. Monoclonal antibodies can potentially be used for biological interventions to regulate serum cholesterol levels.
JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH
(2022)
Review
Biotechnology & Applied Microbiology
Angela Chiew Wen Ch'ng, Paula Lam, Mohammed Alassiri, Theam Soon Lim
Summary: The immune system relies on B- and T-lymphocytes, antibodies, and T-cell receptors to protect the body from invading threats. Antibodies have a more direct role in target recognition compared to T-cell receptors. Despite challenges in displaying TCR on phage surfaces, recombinant versions and modifications have been introduced to facilitate TCR development in phage display.
BIOTECHNOLOGY ADVANCES
(2022)
Correction
Engineering, Chemical
H. K. Melvin Ng, C. P. Leo, Theam Soon Lim, S. C. Low, B. S. Ooi
SEPARATION AND PURIFICATION TECHNOLOGY
(2022)
Article
Multidisciplinary Sciences
Malarvizhi Gurusamy, Denise Tischner, Jingchen Shao, Stephan Klatt, Sven Zukunft, Remy Bonnavion, Stefan Guenther, Kai Siebenbrodt, Roxane-Isabelle Kestner, Tanja Kuhlmann, Ingrid Fleming, Stefan Offermanns, Nina Wettschureck
Summary: The G-protein-coupled receptor P2Y10, expressed in CD4 T cells, mediates RhoA activation and migration in response to lysophosphatidylserine and ATP, which are induced in T cells upon chemokine stimulation through an autocrine/paracrine loop.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Divya Sekar, Christina Dillmann, Evelyn Sirait-Fischer, Annika F. Fink, Aleksandra Zivkovic, Natalie Baum, Elisabeth Strack, Stephan Klatt, Sven Zukunft, Stefan Wallner, Arnaud Descot, Catherine Olesch, Priscila da Silva, Andreas von Knethen, Tobias Schmid, Sabine Groesch, Rajkumar Savai, Nerea Ferreiros, Ingrid Fleming, Sourav Ghosh, Carla Rothlin, Holger Stark, Hind Medyouf, Bernhard Bruene, Andreas Weigert
Summary: Increased levels of ether-phosphatidylserine (ePS) in tumors are associated with tumor-associated macrophage (TAM) expansion and tumor growth. Inhibiting the production of ePS by targeting phosphatidylserine synthase PTDSS1 reduces tumor growth and TAM infiltration.
Editorial Material
Public, Environmental & Occupational Health
Theam Soon Lim, Michael Hust, Livia Visai
FRONTIERS IN PUBLIC HEALTH
(2022)
Editorial Material
Biology
Theam Soon Lim
Summary: Gene editing agents can be delivered using engineered DNA-free virus-like particles (eVLPs) to different organs, leading to improved outcomes in overcoming genetic disorders.
COMMUNICATIONS BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Theam Soon Lim, Yee Siew Choong
Summary: In this study, in silico approaches were used to design specific competitive binders for the receptor binding motif (RBM) of SARS-CoV-2 S-protein. Mutants of the hACE2 peptidase domain (PD) were utilized to increase the binding affinity with RBM. Three PD variants were successfully designed with higher affinity and interaction with SARS-CoV-2-RBM. These designs could potentially serve as a starting point for vaccine/drug development and interfere with the initial recognition between the virus and host cell.
PHYSICAL SCIENCES REVIEWS
(2022)
Article
Cell Biology
Stefan Kuhnert, Siavash Mansouri, Michael A. Rieger, Rajkumar Savai, Edibe Avci, Gabriela Diaz-Pina, Manju Padmasekar, Mario Looso, Stefan Hadzic, Till Acker, Stephan Klatt, Jochen Wilhelm, Ingrid Fleming, Natascha Sommer, Norbert Weissmann, Claus Vogelmeier, Robert Bals, Andreas Zeiher, Stefanie Dimmeler, Werner Seeger, Soni S. Pullamsetti
Summary: This study found an increased incidence of CHIP mutations in COPD patients, which are associated with hypomethylation of PLD5, leading to elevated levels of glycerol phosphocholine, pro-inflammatory cytokines, and deteriorating lung function.
Article
Biochemistry & Molecular Biology
Astrid Weiss, Katharina Alack, Stephan Klatt, Sven Zukunft, Ralph Schermuly, Torsten Frech, Frank-Christoph Mooren, Karsten Krueger
Summary: This study investigated the differences in substrate metabolism between highly trained and untrained individuals using targeted metabolomics. The results showed that endurance-trained individuals exhibited adaptations in lipid metabolism, which may contribute to their lower cardiovascular risk profile.
Article
Biochemistry & Molecular Biology
Angela Chiew Wen Ch'ng, Lena Schepergerdes, Yee Siew Choong, Michael Hust, Theam Soon Lim
Summary: This study focuses on the use of monoclonal antibodies as an alternative antibacterial treatment. It identifies a specific antibody that can inhibit the growth mechanisms of Mycobacterium tuberculosis, potentially providing a solution to antibiotic resistance.
MOLECULAR IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Xiang Li, Fan Wu, Stefan Guenther, Mario Looso, Carsten Kuenne, Ting Zhang, Marion Wiesnet, Stephan Klatt, Sven Zukunft, Ingrid Fleming, Gernot Poschet, Astrid Wietelmann, Ann Atzberger, Michael Potente, Xuejun Yuan, Thomas Braun
Summary: This study reveals that inhibition of fatty acid oxidation in cardiomyocytes promotes cardiomyocyte proliferation and enables heart regeneration. Metabolic studies contribute to understanding the importance of metabolic reprogramming and epigenetic remodeling in this process.
Article
Microbiology
Liam K. R. Sharkey, Romain Guerillot, Calum J. Walsh, Adrianna M. Turner, Jean Y. H. Lee, Stephanie L. Neville, Stephan Klatt, Sarah L. Baines, Sacha J. Pidot, Fernando J. Rossello, Torsten Seemann, Hamish E. G. Mcwilliam, Ellie Cho, Glen P. Carter, Benjamin P. Howden, Christopher A. Mcdevitt, Abderrahman Hachani, Timothy P. Stinear, Ian R. Monk
Summary: This study provides insights into the functionality of the WalKR regulon in Staphylococcus aureus, highlighting its crucial role in cell wall homeostasis, purine biosynthesis, protein biosynthesis, and DNA replication. These findings underscore the potential of WalKR as a target for novel anti-staphylococcal therapeutics.
Article
Chemistry, Multidisciplinary
Xin Qian, Stephan Klatt, Katrin Bennewitz, David Philipp Wohlfart, Bowen Lou, Ye Meng, Michael Buettner, Gernot Poschet, Jakob Morgenstern, Thomas Fleming, Carsten Sticht, Ingrid Hausser, Ingrid Fleming, Julia Szendroedi, Peter Paul Nawroth, Jens Kroll
Summary: This study identifies the enzyme Aldh9a1b as a key player in the detoxification of tt-DDE and elucidates its role in insulin resistance and impaired glucose metabolism. The study also reveals that vascular changes induced by aldh9a1b knockout or tt-DDE treatment can be rescued by insulin receptor sensitizers.
Article
Clinical Neurology
Soumya Mukherjee, Keyla A. Perez, Larissa C. Lago, Stephan Klatt, Catriona A. McLean, Ian E. Birchall, Kevin J. Barnham, Colin L. Masters, Blaine R. Roberts
Summary: Plaques in Alzheimer's disease brains accumulate due to decreased clearance of amyloid-beta peptides which undergo extensive isomerization, particularly at the Asp-1 and Asp-7 residues. Isomerization significantly alters the structure of the peptide, affecting its degradation, oligomer assembly, and the binding of therapeutic antibodies. The accumulation of extensively isomerized amyloid-beta is correlated with the presence of aggregation-prone amyloid-beta(42) in Alzheimer's disease brains.
BRAIN COMMUNICATIONS
(2021)