Review
Biochemistry & Molecular Biology
Mehdi Arbabi-Ghahroudi
Summary: Since the discovery of camelid heavy-chain antibodies in 1993, there has been great interest in the research and application of nanobodies. After years of effort, the first nanobody drug was approved in 2018-2019 for the treatment of rare blood clotting disorders. Despite intellectual property restrictions, nanobodies have the potential to become mainstream biotherapeutics in the future.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemical Research Methods
Meiniang Wang, Likun Wei, Haitao Xiang, Bingzhao Ren, Xiaopan Liu, Lin Jiang, Naibo Yang, Jiahai Shi
Summary: This study demonstrates the construction and application of a megadiverse naive sdAb library derived from non-immunized camelid animals. The library provides a rapid and adaptable platform for antibody creation, yielding high-affinity VHH candidates with therapeutic and diagnostic implications.
ANALYTICAL BIOCHEMISTRY
(2022)
Article
Medicine, Research & Experimental
Sanne A. M. van Lith, Fokko J. Huizing, Gerben M. Franssen, Bianca A. W. Hoeben, Jasper Lok, Sofia Doulkeridou, Otto C. Boerman, Martin Gotthardt, Paul M. P. van Bergen en Henegouwen, Johan Bussink, Sandra Heskamp
Summary: This study compared variants of CAIX-binding VHH B9 with different affinities (low and high) for SPECT imaging of CAIX expression. The results showed that B9 variants with ABD demonstrated better tumor uptake, but some uptake was CAIX-independent, limiting their use in hypoxia assessment.
MOLECULAR PHARMACEUTICS
(2022)
Review
Oncology
Yasaman Asaadi, Fatemeh Fazlollahi Jouneghani, Sara Janani, Fatemeh Rahbarizadeh
Summary: By comparing the structure and properties of camelid antibodies (VHHs) and single-chain variable fragments (scFvs), it can be determined which one is more suitable for their respective therapeutic, diagnostic, and research applications.
BIOMARKER RESEARCH
(2021)
Review
Cell Biology
Jan Gettemans, Brian De Dobbelaer
Summary: Single-domain antibodies derived from camelids and sharks, known as nanobodies, have gained attention for their high specificity and affinity binding to targets. Their key features including single-domain nature, small size, affordable high-level expression, and flexibility in altering primary structure have made them appealing for researchers and valuable in biomedical research.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2021)
Article
Immunology
Wenjuan Du, Rick Janssens, Anna Z. Mykytyn, Wentao Li, Dubravka Drabek, Rien van Haperen, Marianthi Chatziandreou, Melanie Rissmann, Joline van der Lee, Melissa van Dortmondt, Itziar Serna Martin, Frank J. M. van Kuppeveld, Daniel L. Hurdiss, Bart L. Haagmans, Frank Grosveld, Berend-Jan Bosch
Summary: A six-antigen binding site biparatopic heavy-chain-only antibody is designed, which shows potent neutralizing activity against SARS-CoV-2 and Omicron variants, and protects against SARS-CoV-2 infection in a hamster model.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Virology
Daria V. Voronina, Dmitry Shcheblyakov, Irina A. Favorskaya, Ilias B. Esmagambetov, Alina S. Dzharullaeva, Amir Tukhvatulin, Olga Zubkova, Olga Popova, Vladislav Y. Kan, Alina S. Bandelyuk, Maxim M. Shmarov, Denis Y. Logunov, Boris S. Naroditskiy, Aleksandr L. Gintsburg
Summary: This study modified two potent single-domain antibodies to enhance their antiviral activity against multiple influenza subtypes, demonstrating effective prophylaxis and therapy in mice.
Article
Biochemistry & Molecular Biology
Seisho Kinoshita, Makoto Nakakido, Chinatsu Mori, Daisuke Kuroda, Jose M. M. Caaveiro, Kouhei Tsumoto
Summary: Research on VHH engineering for biotechnological and clinical applications is actively conducted to take advantage of their favorable biophysical properties. Humanization of camelid VHHs through CDR grafting with a humanized VHH in clinical trials resulted in changes to the affinity, thermal stability, and conformational structure. Mutational and back-mutational analyses on the framework regions revealed the significant contribution of bulky residues and intramolecular interactions to the properties of VHHs. Back-mutations restored intramolecular interactions, resulting in increased thermal stability and affinity, showing the potential for designing VHHs by modifying the framework region without altering the CDRs.
Review
Biochemistry & Molecular Biology
Wenyi Wang, Jumao Yuan, Changan Jiang
Summary: Nanobodies, variable domains of heavy chain-only antibodies isolated from camelids, exhibit unique features such as small size, high stability, and cryptic epitopes accessibility, making them ideal for advanced applications in plants and animals. Current applications of nanobodies in plant science and biotechnology include expression in plants, biotechnological applications, toxin and pathogen determination, and resistance against plant pathogens. Prospects and challenges of nanobody applications in plants are also discussed in this review.
PLANT MOLECULAR BIOLOGY
(2021)
Article
Oncology
Yan Yan, Xiao Cheng, Lin Li, Rumeng Zhang, Yong Zhu, Zhengsheng Wu, Keshuo Ding
Summary: The study successfully constructed HER2-nanobody and demonstrated its ability to inhibit growth and promote apoptosis of HER2-positive breast cancer cells. HER2-nanobody exerts its tumor suppressive role by inhibiting the phosphorylation of ERK and AKT.
FRONTIERS IN ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Seisho Kinoshita, Makoto Nakakido, Chinatsu Mori, Daisuke Kuroda, Jose M. M. Caaveiro, Kouhei Tsumoto
Summary: Camelid single domain antibodies, known as VHHs or Nanobodies, are versatile tools for various biotechnological and clinical applications due to their favorable biophysical properties. Research on VHH engineering has shown that modifications can impact affinity and thermal stability, highlighting the importance of interactions between the framework region and CDR3 for regulating VHH characteristics.
Review
Biochemistry & Molecular Biology
Angela Donato Maia Malaquias, Livia Erika Carlos Marques, Soraya S. Pereira, Cleberson de Freitas Fernandes, Andrea Queiroz Maranhao, Rodrigo G. Stabeli, Eridan Orlando Pereira Tramontina Florean, Maria Izabel Florindo Guedes, Carla Freire Celedonio Fernandes
Summary: VHHs are small functional immunoglobulins that exhibit high tissue penetration and low immunogenicity. They provide superior antigen recognition compared to human antibodies, along with better solubility and stability. Plant-based expression systems offer versatility, cost-effectiveness, safety, and efficiency in producing VHH-related constructs.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Biophysics
Yong-Yi Zhang, Li-Hua Li, Yu Wang, Hong Wang, Zhen-Lin Xu, Yuan-Xin Tian, Yuan-Ming Sun, Jin-Yi Yang, Yu-Dong Shen
Summary: The study developed an ultrasensitive fluorescence immunochromatographic assay strip for rapid and quantitative detection of paraquat. The strip showed high sensitivity and stability, and could be used for quantitative analysis with a strip reader and semi-quantitative analysis with the naked eye.
BIOSENSORS & BIOELECTRONICS
(2022)
Article
Immunology
Eugenia A. Panova, Denis A. Kleymenov, Dmitry V. Shcheblyakov, Evgeniia N. Bykonia, Elena P. Mazunina, Alina S. Dzharullaeva, Anastasia N. Zolotar, Artem A. Derkaev, Ilias B. Esmagambetov, Ivan I. Sorokin, Evgeny V. Usachev, Anatoly N. Noskov, Igor A. Ivanov, Timofei S. Zatsepin, Sergey E. Dmitriev, Vladimir A. Gushchin, Boris S. Naroditsky, Denis Y. Logunov, Alexander L. Gintsburg
Summary: Single-domain antibodies (sdAbs, VHHs, or nanobodies) are small-sized antibodies that show promise in treating infectious and somatic diseases. Their ability to bind hard-to-reach antigenic epitopes makes them valuable for therapy. Fusion of VHH with the immunoglobulin Fc fragment enhances their neutralizing activity and half-life.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Jessica Hong, Hyung Joon Kwon, Raul Cachau, Catherine Z. Chen, Kevin John Butay, Zhijian Duan, Dan Li, Hua Ren, Tianyuzhou Liang, Jianghai Zhu, Venkata P. Dandey, Negin P. Martin, Dominic Esposito, Uriel Ortega-Rodriguez, Miao Xu, Mario J. Borgnia, Hang Xie, Mitchell Ho
Summary: The study constructed large dromedary camel VHH phage libraries and successfully isolated two high-affinity nanobodies that showed broad neutralization activity against SARS-CoV-2 and its variants. These nanobodies can be used for therapeutic purposes against COVID-19 variants, and the dromedary camel VHH phage libraries serve as a unique platform for rapidly isolating potent nanobodies against future emerging viruses.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Serge Muyldermans
Summary: Nanobodies, a trademark of Ablynx, are single antigen-binding domains of heavy chain-only antibodies in Camelidae produced recombinantly for research and medical applications. Various methods are used for their generation, producing cost-effective Nbs with high affinity for their target antigens. Additionally, engineering technologies have been explored to broaden the application range of Nbs for potential advantages over other affinity reagents.
Review
Biochemistry & Molecular Biology
Raf Van Campenhout, Serge Muyldermans, Mathieu Vinken, Nick Devoogdt, Timo W. M. De Groof
Summary: Cell plasma membrane proteins play a crucial role in cell regulation, with transport proteins facilitating molecule and ion exchange. The dysfunction of these proteins can lead to various human pathologies, making them potential therapeutic targets. Nanobodies show promise in targeting and modulating the activity of these proteins, offering a potential approach in drug development.
Article
Agriculture, Dairy & Animal Science
Edson Kinimi, Serge Muyldermans, Cecile Vincke, Steven Odongo, Richard Kock, Satya Parida, Mana Mahapatra, Gerald Misinzo
Summary: Peste des petits ruminants virus (PPRV) causes a devastating disease in sheep and goats, threatening food security and conservation efforts. Innovative diagnostic tools, such as nanobodies derived from camelid antibodies, show promise in rapidly identifying PPRV.
Article
Chemistry, Analytical
Stanislav Trashin, Francisco Morales-Yanez, Saranya Thiruvottriyur Shanmugam, Linda Paredis, Erik N. Carrion, Idalia Sariego, Serge Muyldermans, Katja Polman, Sergiu M. Gorun, Karolien De Wael
Summary: A new method for detecting the antigen marker of human toxocariasis is proposed, utilizing a rapid sandwich immunoassay sensor that achieves high sensitivity to pg/mL levels through a redox cycle involving photocatalytic oxidation and electrochemical reduction steps.
ANALYTICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Yaozhong Hu, Ema Romao, Cecile Vincke, Lea Brys, Yvon Elkrim, Marylene Vandevenne, Changxiao Liu, Serge Muyldermans
Summary: Uncontrolled growth of solid tumors can lead to hypoxic conditions and activation of HIF-1 alpha, promoting metabolism, proliferation, and metastasis of tumor cells. Inhibiting the transcriptional activity of HIF-1 could be a potential strategy for cancer therapy. Nbs selected through phage display showed significant inhibitory effects on the transcriptional activity of HIF-1, confirming their potential in cancer treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Philippe J-L Y. Gevenois, Pieter De Pauw, Steve Schoonooghe, Cedric Delporte, Thami Sebti, Karim Amighi, Serge Muyldermans, Nathalie Wauthoz
Summary: IL-13, a pleiotropic cytokine mainly secreted by Th2 cells, has been extensively studied for its role in conditions involving allergy, inflammation, and fibrosis. While traditional anti-IL-13 mAbs have not shown significant improvement in human trials, nanobodies derived from camelid H chain-only Abs have shown promise in targeted therapy with improved affinity and biological activity.
JOURNAL OF IMMUNOLOGY
(2021)
Review
Medical Laboratory Technology
Tahir S. Pillay, Serge Muyldermans
Summary: Antibodies have been pivotal in diagnostic methods, transitioning from polyclonal to monoclonal antibodies, and now to single-domain antibodies like nanobodies. This evolution has greatly enhanced diagnostic accuracy and simplified processes of protein re-engineering and expression.
ANNALS OF LABORATORY MEDICINE
(2021)
Article
Agriculture, Dairy & Animal Science
Edson Kinimi, Mana Mahapatra, Tebogo Kgotlele, Mariam R. Makange, Chandana Tennakoon, Felix Njeumi, Steven Odongo, Serge Muyldermans, Richard Kock, Satya Parida, Mark Rweyemamu, Gerald Misinzo
Summary: PPRV virus causes a devastating disease in sheep and goats, and Oxford nanopore MinION sequencing technology shows promise in quickly generating complete genomes for diagnostic and surveillance purposes, especially in developing countries. Larger field studies are needed to assess the robustness of this technology for PPR control and eradication efforts.
Article
Food Science & Technology
Yaozhong Hu, Chuan Zhang, Feier Yang, Jing Lin, Yi Wang, Sihao Wu, Ying Sun, Bowei Zhang, Huan Lv, Xuemeng Ji, Yang Lu, Serge Muyldermans, Shuo Wang
Summary: This study demonstrated the selection of Nbs against allergen with crude protein content to develop the immunoassay for lupine surveillance in foods. The developed sandwich ELISA showed a linear range of 0.036-4.4 mu g/mL with a detection limit of 1.15 ng/mL, confirming the effectiveness of the immunoassay. The immunoassay was further validated by detecting samples with spiked allergen, showing a recovery rate of 86.25% to 108.45% with a coefficient of variation (CV) less than 4.0%.
Article
Chemistry, Analytical
Rasel A. Al-Amin, Phathutshedzo M. Muthelo, Eldar Abdurakhmanov, Cecile Vincke, Shahnaz P. Amin, Serge Muyldermans, U. Helena Danielson, Ulf Landegren
Summary: High-quality affinity probes are essential for protein detection. Nanobodies have been explored as alternative affinity reagents to polyclonal antibodies. The efficient site-specific method described in this study allows the preparation of high-quality oligo-conjugated nanobody probes, which demonstrate improved performance in proximity extension assays (PEA) compared to polyclonal antibody probes.
ANALYTICAL CHEMISTRY
(2022)
Review
Agriculture, Multidisciplinary
Yaozhong Hu, Yi Wang, Jing Lin, Sihao Wu, Serge Muyldermans, Shuo Wang
Summary: The unique characteristics of camelid heavy-chain only antibodies (HCAb) derived nanobodies (Nbs) have led to their widespread application in various fields. However, their application in food allergen inspection and immunotherapy has been lacking. Nbs possess strong properties and a simple selecting strategy, making them advantageous for immunoassays and as blocking antibodies. The development of specific Nbs against food allergens shows their potential in food allergen surveillance and immunotherapy.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Yaozhong Hu, Jing Lin, Yi Wang, Sihao Wu, Jing Wu, Huan Lv, Xuemeng Ji, Serge Muyldermans, Yan Zhang, Shuo Wang
Summary: This study generated SF-specific nanobodies and demonstrated their potential as diagnostic immunoassay tools.
Article
Biochemistry & Molecular Biology
Lan-Huong Tran, Geert-Jan Graulus, Cecile Vincke, Natalia Smiejkowska, Anne Kindt, Nick Devoogdt, Serge Muyldermans, Peter Adriaensens, Wanda Guedens
Summary: Ovarian cancer ranks fifth in cancer-related deaths among women, often diagnosed at an advanced stage. Nanobodies targeting ovarian cancer biomarkers have strong binding affinity and high specificity, showing potential for early detection.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biotechnology & Applied Microbiology
Giulia Monti, Cecile Vincke, Melanie Lunding, Anne Mette G. Jensen, Peder Madsen, Serge Muyldermans, Mads Kjolby, Olav M. Andersen
Summary: In this study, we purified and characterized eight Nbs that specifically recognize SORLA with high affinity. These Nbs have the potential to be used in disease clarifying research and clinical diagnostics.
JOURNAL OF BIOTECHNOLOGY
(2023)
Review
Biotechnology & Applied Microbiology
Marcus Petersson, Sandra W. Thrane, Lone Gram, Serge Muyldermans, Andreas H. Laustsen
TRENDS IN BIOTECHNOLOGY
(2023)