Review
Immunology
Kristian Daniel Ralph Roth, Esther Veronika Wenzel, Maximilian Ruschig, Stephan Steinke, Nora Langreder, Philip Alexander Heine, Kai-Thomas Schneider, Rico Ballmann, Viola Fuehner, Philipp Kuhn, Thomas Schirrmann, Andre Frenzel, Stefan Duebel, Maren Schubert, Gustavo Marcal Schmidt Garcia Moreira, Federico Bertoglio, Giulio Russo, Michael Hust
Summary: Antibodies are crucial for the diagnosis and treatment of diseases caused by pathogens. Their importance has been highlighted during the COVID-19 pandemic, and new technologies like antibody phage display have advanced the discovery of human monoclonal antibodies for therapeutic purposes. These technologies have expanded the possibilities for generating antibodies against a wide range of pathogens and toxins.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Biochemical Research Methods
Charlotte Rimbault, Pelle D. Knudsen, Anna Damsbo, Kim Boddum, Hanif Ali, Celeste M. Hackney, Lars Ellgaard, Markus -Frederik Bohn, Andreas H. Laustsen
Summary: Phage display technology is a powerful tool for selecting monoclonal antibodies against a diverse set of antigens. However, generating monoclonal antibodies against animal toxins is challenging due to difficulties in obtaining them from venom. This study successfully expressed alpha-cobratoxin in E. coli and used it as an antigen in a phage display selection campaign, resulting in the isolation of a scFv with similar binding affinity to a control scFv against the native toxin. The selected scFv inhibits the interaction between the acetylcholine receptor and the native toxin in vitro, representing the first entirely in vitro antibody selection strategy for generating neutralizing monoclonal antibodies against a snake toxin.
Article
Biophysics
Olga I. Guliy, Stella S. Evstigneeva, Lev A. Dykman
Summary: Antibody phage display is a useful technique for producing antibodies to specific antigens, replacing the traditional hybrid-oma technology. It simplifies the process by manipulating DNA and bacteria, shortening the time and reducing the cost of antibody production. Antibodies prepared through phage display can be used as selective receptors in biosensors.
BIOSENSORS & BIOELECTRONICS
(2023)
Article
Multidisciplinary Sciences
Justina Rutkauskaite, Simon Berger, Stavros Stavrakis, Oliver Dressler, John Heyman, Xavier Casadevall i Solvas, Andrew deMello, Linas Mazutis
Summary: In this study, a droplet microfluidic approach was developed for high-throughput screening and sorting of antibody-secreting cells. The method utilizes Forster resonance electron transfer (FRET) signal to mediate the binding of antibodies and probes, enabling functional characterization of individual cells. The system efficiently screens antigen-specific cells and provides important data on antibody secretion rate and membrane-bound fraction.
Article
Biology
Taishi Kondo, Kazuhiro Matsuoka, Shun Umemoto, Tomoshige Fujino, Gosuke Hayashi, Yasumasa Iwatani, Hiroshi Murakami
Summary: In this study, affinity maturation of monobodies against SARS-CoV-2 spike protein and their neutralizing activity against several variants were reported. One monobody showed extremely high affinity and efficiently neutralized multiple variants. These monobodies could be useful for neutralizing current and future SARS-CoV-2 variants.
LIFE SCIENCE ALLIANCE
(2022)
Article
Multidisciplinary Sciences
Junxia Wang, Liang Li, Yingkun Zhang, Kaifeng Zhao, Xiaofeng Chen, Haicong Shen, Yuanqiang Chen, Jia Song, Yuqiang Ma, Chaoyong Yang, Hongming Ding, Zhi Zhu
Summary: Efficient molecular selection is crucial for various biomedical applications. By utilizing deterministic lateral-displacement microfluidics, the equilibrium of dissociation can be greatly shifted, leading to improved selection efficiency and better discrimination of ligand affinity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Pharmacology & Pharmacy
Sandra Isabel Aguiar, Joana N. R. Dias, Ana Santos Andre, Marta Lisete Silva, Diana Martins, Belmira Carrapico, Miguel Castanho, Joao Carrico, Marco Cavaco, Maria Manuela Gaspar, Rui Jorge Nobre, Luis Pereira de Almeida, Soraia Oliveira, Lurdes Gano, Joao D. G. Correia, Carlos Barbas, Joao Goncalves, Vera Neves, Frederico Aires-da-Silva
Summary: The major bottleneck in CNS drug development is the discovery of molecules that can cross BBB. Using nano-delivery strategies and in vivo cell immunization to construct sdAb library targeting BBB endothelial cell receptors, specific nano-antibody scaffolds with promising properties for brain targeting and drug delivery were successfully selected.
Article
Biochemical Research Methods
Joana Sales-Dias, Andreia Ferreira, Marcia Lamy, Giacomo Domenici, Sandra M. S. Monteiro, Antonio Pires, Ana R. Lemos, Khrystyna Kucheryava, Ligia S. Nobre, Pedro M. F. Sousa, Tiago M. Bandeiras, Gabriela Silva, Ana Barbas
Summary: Development of specific functional blocking anti-DLL1 antibodies with potential activity against ER+ breast cancer cells was reported, suggesting the potential for identifying anti-DLL1 antibodies candidates against breast cancer using this strategy.
Article
Multidisciplinary Sciences
Nora Langreder, Dorina Schaeckermann, Doris Meier, Marlies Becker, Maren Schubert, Stefan Duebel, Thomas Reinard, Stefanie Figge-Wegener, Kristine Rossbach, Wolfgang Baeumer, Simone Ladel, Michael Hust
Summary: Insect bite hypersensitivity (IBH), the most common allergic skin disease in horses, is caused by bites from Culicoides spp. insects, resulting in a type I/IVb allergy involving eosinophil cells. A potential treatment option is the use of a therapeutic antibody targeting equine interleukin 5, the main activator and regulator of eosinophils. Through phage display and in vitro affinity maturation, an antibody named NOL226-2-D10 was developed, showing strong inhibition of interleukin 5 binding and satisfactory producibility. This antibody is a promising candidate for in vivo studies to treat equine IBH.
SCIENTIFIC REPORTS
(2023)
Article
Plant Sciences
Adel M. Zakri, Abdullah A. Al-Doss, Ahmed A. Ali, Emad M. Samara, Basem S. Ahmed, Mohammed A. Al-Saleh, Ali M. Idris, Omar A. Abdalla, Markus Sack
Summary: This study isolated two camel-derived nanobodies against Tomato leaf curl Sudan virus (ToLCSDV) using phage display technology. The nanobodies also cross-reacted with Tomato yellow leaf curl virus and showed significant enzyme-linked immunosorbent assay reactivity with plants infected with typical begomovirus symptoms. These results pave the way for developing diagnostics for begomovirus detection, design of novel nanomaterials based on virus-like particles, and nanobody-mediated begomovirus resistance in economically important crops.
Article
Chemistry, Multidisciplinary
David N. Philpott, Surath Gomis, Hansen Wang, Randy Atwal, Abdellali Kelil, Tanja Sack, Brandon Morningstar, Chris Burnie, Edward H. Sargent, Stephane Angers, Sachdev Sidhu, Shana O. Kelley
Summary: The rapid on-cell phage display platform presented in this study accelerates the development of high-performance human antibodies by mimicking the complex in vivo binding environment, improving screening efficiency and accuracy.
ACS CENTRAL SCIENCE
(2022)
Review
Chemistry, Multidisciplinary
Michael A. Firer, Galia Luboshits
Summary: The development and clinical efficacy of ADCs have attracted significant interest in academia and industry, with ten ADCs having received FDA approval. These drugs specifically deliver cytotoxic agents to target cells, showing promise in providing long-term clinical benefits for patients with hematological malignancies.
ADVANCED FUNCTIONAL MATERIALS
(2021)
Article
Nanoscience & Nanotechnology
Ni Meng, Xiaolong Cheng, Mengyao Sun, Yushan Zhang, Xueke Sun, Xifu Liu, Jing Chen
Summary: This study identified specific nanobodies targeting the monkeypox virus protein A35R, which can serve as potential candidates for the development of monkeypox vaccines and diagnostic kits. The nanobodies displayed high affinity and specificity for A35R, laying the foundation for further research and applications in diagnosing and treating monkeypox.
INTERNATIONAL JOURNAL OF NANOMEDICINE
(2023)
Article
Chemistry, Multidisciplinary
Thae Thae Min, Montarop Yamabhai
Summary: The study developed two specific human antibacterial scFv using phage display antibody technology, which can be applied for the specific recognition and treatment of bacteria. It is a promising recombinant nanostructure with potential applications in detecting and treating bacterial infections.
Article
Immunology
Shanshan Peng, Syed Husnain Raza Shah, Shengsheng Mei, Eu Gene Vong, Yisheng Sun, Jinbiao Zhan
Summary: The discovery of anti-RBD single-chain antibodies that effectively combat SARS-CoV-2-induced acute lung injury (ALI) is of significant importance in the development of potential antibody treatments and reduction of inflammatory responses.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ye Zhou, Nykola C. Jones, Jannik Nedergaard Pedersen, Bianca Perez, Soren Vronning Hoffmann, Steen Vang Petersen, Jan Skov Pedersen, Adam Perriman, Peter Kristensen, Renjun Gao, Zheng Guo
Article
Biochemistry & Molecular Biology
Bekir Engin Eser, Michal Poborsky, Rongrong Dai, Shigenobu Kishino, Anita Ljubic, Michiki Takeuchi, Charlotte Jacobsen, Jun Ogawa, Peter Kristensen, Zheng Guo
Article
Biochemistry & Molecular Biology
Rasmus Kold-Christensen, Karina Kragh Jensen, Emil Smedegard-Holmquist, Lambert Kristiansen Sorensen, Jakob Hansen, Karl Anker Jorgensen, Peter Kristensen, Mogens Johannsen
Review
Engineering, Chemical
Yan Zhang, Bekir Engin Eser, Peter Kristensen, Zheng Guo
CHINESE JOURNAL OF CHEMICAL ENGINEERING
(2020)
Article
Biotechnology & Applied Microbiology
Yan Zhang, Bekir Engin Eser, Georgios Kougioumtzoglou, Zekiye Eser, Michal Poborsky, Shigenobu Kishino, Michiki Takeuchi, Jun Ogawa, Peter Kristensen, Zheng Guo
Summary: This research investigates the regioselectivity of fatty acid hydratase-mediated hydroxy fatty acid production, achieving a broader conversion of substrates through amino acid mutations and residue variations, further optimizing the high-value products.
BIOCHEMICAL ENGINEERING JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Yan Zhang, Niels Mikkel Dyrby Breum, Sune Schubert, Negin Hashemi, Rikke Kyhnau, Marius Sandholt Knauf, Masuthan Mathialakan, Michiki Takeuchi, Shigenobu Kishino, Jun Ogawa, Peter Kristensen, Zheng Guo, Bekir Engin Eser
Summary: Research on semi-rational protein engineering to alter the binding site residues of Lactobacillus Acidophilus' fatty acid hydratase-1 for improved regioselectivity; although not achieving a completely new regioselectivity, a shift towards cis-5, cis-8, cis-11, cis-14, cis-17-eicosapentaenoic acid was observed; mutants like S393/S395 showed excellent regioselectivity, producing a single hydroxy fatty acid product, which is advantageous from an application standpoint.
Article
Chemistry, Multidisciplinary
Wei Fan, Tao Du, Aida Droce, Lars R. Jensen, Randall E. Youngman, Xiangting Ren, Leonid Gurevich, Mathieu Bauchy, Peter Kristensen, Bengang Xing, Donghong Yu, Morten M. Smedskjaer
Summary: This study investigates the deformation and fracture behavior of inorganic-polymer hybrids and finds that the noncovalent intermolecular interactions between polymer and silica networks play a crucial role. The study also explores three methods to improve the balance between strength and toughness of the hybrids and demonstrates the optimized mechanical properties and biocompatibility of the hybrid material.
Article
Biochemistry & Molecular Biology
Josephine Geertsen Keller, Kirstine Mejlstrup Hymoller, Maria Eriksen Thorsager, Noriko Y. Hansen, Jens Uldum Erlandsen, Cinzia Tesauro, Anne Katrine W. Simonsen, Anne Bech Andersen, Kamilla Vands-Petersen, Lise Lolle Holm, Magnus Stougaard, Brage Storstein Andresen, Peter Kristensen, Rikke Frohlich, Birgitta R. Knudsen
Summary: The function of human topoisomerase 1 (TOP1) in regulating G-quadruplex (G4) formation in the MYC P1 promoter has been investigated, revealing its involvement in the regulation of G4 formation and its potential as a regulator in gene expression.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Chemistry, Analytical
Andreas Madsen, Oscar Mejias-Gomez, Lasse E. Pedersen, Kerstin Skovgaard, Peter Kristensen, Steffen Goletz
Summary: Simultaneous targeting of different antigens with bispecific antibodies (bsAbs) has high therapeutic potential but presents challenges in analysis. Flow-induced dispersion analysis (FIDA) allows in-depth characterization of bsAbs under near-native conditions, determining equilibrium dissociation constants and analyzing binding cooperativity. FIDA is a versatile tool with low material consumption and high matrix tolerability for format selection and characterization of complex protein therapeutics.
ANALYTICAL CHEMISTRY
(2022)
Article
Medicine, Research & Experimental
Andreas V. Madsen, Peter Kristensen, Alexander K. Buell, Steffen Goletz
Summary: This study demonstrates a simple and efficient method to generate high-quality bsAbs with both binding functionalities intact by fusing sdAbs onto IgG scaffolds through flexible linkers. By systematically comparing sdAb fusion strategies, the results show that fusion of sdAbs to the heavy chain promotes good expression, stability, and efficient binding to both antigens. The study also provides a toolbox of complementary methods for in-depth analysis of key features, such as dual antigen binding and stability, to ensure high bsAb quality.
Article
Chemistry, Analytical
Jinhua Dong, Bhagat Banwait, Hiroshi Ueda, Peter Kristensen
Summary: Quenchbodies, a type of biosensor, use antibodies labeled with a fluorescent dye to detect proteins. The dye is quenched in the absence of an antigen, but de-quenched in its presence. This study demonstrates the development of mini Q-bodies using a single-domain heavy chain V-H antibody and different dyes. The results confirm the applicability of this method in detecting proteins.
Article
Medicine, Research & Experimental
Oscar Mejias-Gomez, Andreas V. Madsen, Kerstin Skovgaard, Lasse E. Pedersen, J. Preben Morth, Timothy P. Jenkins, Peter Kristensen, Steffen Goletz
Summary: This study analyzes human antibody sequences to understand the factors determining antibody diversity and specificity. The study reveals the importance of specific residue positions and their influence on antibody characteristics. These findings have significant implications for the development and optimization of antibody therapeutics.
Article
Biochemical Research Methods
Oscar Mejias-Gomez, Andreas V. Madsen, Lasse E. Pedersen, Peter Kristensen, Steffen Goletz
Summary: This study presents a system based on split beta-lactamase complementation, which can remove OFF-frame clones and increase functional diversity more quickly and efficiently, suitable for constructing randomized libraries. The system can eliminate OFF-frame clones containing stop codons or frameshifts in starting mixtures, enriching the IN-frame clones to about 70%.
Meeting Abstract
Chemistry, Applied
Yan Zhang, Bekir E. Eser, Zheng Guo
JOURNAL OF THE AMERICAN OIL CHEMISTS SOCIETY
(2020)
Article
Chemistry, Analytical
Andreas Madsen, Oscar Mejias-Gomez, Lasse E. Pedersen, Kerstin Skovgaard, Peter Kristensen, Steffen Goletz
Summary: FIDA technology enables in-depth characterization of bsAbs with diverse molecular architectures and valencies, analyzing their bispecific binding functionality without being affected by molecular format, making it a versatile tool for selecting and characterizing complex protein therapeutics.
ANALYTICAL CHEMISTRY
(2022)