Article
Biotechnology & Applied Microbiology
Qianlin Li, Fuqiang Zhang, Yi Lu, Huan Hu, Jin Wang, Cheng Guo, Qiang Deng, Conghui Liao, Qin Wu, Tingsong Hu, Zeliang Chen, Jiahai Lu
Summary: In this study, we developed potent multivalent VHH antibodies targeting the E2 glycoprotein of CHIKV, with Nb-2E8 and Nb-3C5 showing high-affinity binding within the nanomolar range.
JOURNAL OF NANOBIOTECHNOLOGY
(2022)
Article
Multidisciplinary Sciences
Jules B. Weinstein, Timothy A. Bates, Hans C. Leier, Savannah K. McBride, Eric Barklis, Fikadu G. Tafesse
Summary: Researchers have identified an alpaca-derived antibody fragment, saRBD-1, that can competitively bind to the receptor-binding domain of the spike protein in SARS-CoV-2, thus disrupting the virus's ability to infect human cells. They have also developed a bivalent nanobody construct that can block infection at very low concentrations and remains effective against emerging variants of the virus.
Article
Immunology
Hari P. Dulal, David J. Vance, Durga P. Neupane, Xiangcheng Chen, Jacqueline M. Tremblay, Charles B. Shoemaker, Nicholas J. Mantis, Jeongmin Song
Summary: Researchers generated a VHH antibody library from typhoid toxoid-immunized alpacas and identified six potent antibodies that can neutralize typhoid toxin and protect mice from its toxicity.
INFECTION AND IMMUNITY
(2022)
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)
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
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
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)
Review
Biochemistry & Molecular Biology
Martin A. Rossotti, Kasandra Belanger, Kevin A. Henry, Jamshid Tanha
Summary: Single-domain antibodies have desirable properties as biologic drugs, but their sequences may increase immunogenicity risks. While most clinical trials show minimal immunogenicity, special caution is needed for highly potent sdAbs. Further research is needed to establish humanization thresholds to maximize human sequence content without compromising binding affinity or stability.
Article
Microbiology
Greg Hussack, Martin A. Rossotti, Henk van Faassen, Tomohiko Murase, Luiz Eugenio, Joseph D. Schrag, Kenneth K. -S. Ng, Jamshid Tanha
Summary: Crystal structures of camelid heavy-chain antibody variable domains (V(H)Hs) bound to fragments of the combined repetitive oligopeptides domain of Clostridiodes difficile toxin A (TcdA) revealed a spatial arrangement between VHH A20 and VHH A26. Based on this observation, a biparatopic fusion protein A20-A26 was generated, which showed improved binding affinity and neutralization potency compared to unfused A20 and A26 V(H)Hs. A20-A26 demonstrated higher potency than various control constructs. Size-exclusion chromatography-multiangle light scattering (SEC-MALS) analysis confirmed the 1:1 stoichiometry and simultaneous engagement of both A20 and A26 epitopes by A20-A26, in contrast to the varied and heterogeneous binding modes of control constructs. These results underscore the importance of molecular geometric constraints in generating highly potent antibody-based reagents.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Nutrition & Dietetics
Aya Umeno, Toshiki Fukui, Yoshiko Hashimoto, Masatoshi Kataoka, Yoshihisa Hagihara, Hidenori Nagai, Masanori Horie, Mototada Shichiri, Kohzoh Yoshino, Yasukazu Yoshida
JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION
(2018)
Article
Biochemistry & Molecular Biology
Takeru Suzuki, Yuki Mochizuki, Shinnosuke Kimura, Yoko Akazawa-Ogawa, Yoshihisa Hagihara, Naoto Nemoto
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2018)
Article
Biochemistry & Molecular Biology
Masahiro Noji, Masatomo So, Keiichi Yamaguchi, Hironobu Hojo, Maki Onda, Yoko Akazawa-Ogawa, Yoshihisa Hagihara, Yuji Goto
Article
Biochemistry & Molecular Biology
Kalpana Nautiyal, Md Golam Kibria, Yoko Akazawa-Ogawa, Yoshihisa Hagihara, Yutaka Kuroda
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2019)
Article
Multidisciplinary Sciences
Takako Saito, Ikuo Wada, Naokazu Inoue
SCIENTIFIC REPORTS
(2019)
Article
Biochemistry & Molecular Biology
Takako Saito, Ikuo Wada, Naokazu Inoue
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2019)
Article
Biochemistry & Molecular Biology
Yoko Akazawa-Ogawa, Yasuo Komatsu, Yoshihiro Nakajima, Naoshi Kojima, Yoshihisa Hagihara
JOURNAL OF BIOCHEMISTRY
(2020)
Article
Developmental Biology
Naokazu Inoue, Takako Saito, Ikuo Wada
Article
Multidisciplinary Sciences
Ryoichi Ono, Masahiro Masuya, Naokazu Inoue, Makoto Shinmei, Satomi Ishii, Yuri Maegawa, Bishnu Devi Maharjan, Naoyuki Katayama, Tetsuya Nosaka
Summary: The TET1 gene encodes an epigenetic modifying molecule involved in demethylation of 5-methylcytosine and is highly expressed in some hematological malignancies, but may not be critical for myeloid leukemogenesis caused by MLL-ENL. Careful assessment may be needed for therapeutic application of TET1 inhibition.
Article
Biology
Naokazu Inoue, Yoshihisa Hagihara, Ikuo Wada
Summary: The study demonstrates the essential role of evolutionarily conserved factors DCST1 and DCST2 in sperm-egg fusion in mice, and how the protein stability of SPACA6 is regulated differently by DCST1/2 and IZUMO1. This suggests that spermatozoa ensure proper fertilization in mammals by integrating various molecular pathways, including an evolutionarily conserved system developed over nearly one billion years of evolution.
Article
Pharmacology & Pharmacy
Md. Golam Kibria, Yoko Akazawa-Ogawa, Yoshihisa Hagihara, Yutaka Kuroda
Summary: The study demonstrates that immunization with amorphous aggregates of a misfolded VHH can induce a strong serum IgG response against VHH-7D12 antibodies, with a specific focus on the CDRs. The long-term immune response established a strong memory response against native VHH-7D12, but a weaker response against native VHH analogs.
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2021)
Article
Biochemistry & Molecular Biology
Naokazu Inoue, Yuhkoh Satouh, Ikuo Wada
Summary: IZUMO family member 3 (IZUMO3) plays a crucial role in acrosome biogenesis, and its loss results in malformed spermatozoa and male subfertility. Therefore, the involvement of IZUMO3 in spermiogenesis requires elaborate acrosome formation.
MOLECULAR REPRODUCTION AND DEVELOPMENT
(2021)
Article
Biochemistry & Molecular Biology
Md Golam Kibria, Akari Fukutani, Yoko Akazawa-Ogawa, Yoshihisa Hagihara, Yutaka Kuroda
Summary: The study found that under thermal stress conditions, lysine SEP tags have a more potent solubilization effect compared to arginine SEP tags, with no impact on the structural and functional properties of the protein.
Article
Biology
Naokazu Inoue
Summary: Gamete fusion, the final event of fertilization, involves a complex intermolecular reaction to ensure species specificity. Many factors are involved in this process, but their specific contributions remain largely unknown.
Article
Nutrition & Dietetics
Mototada Shichiri, Noriko Ishida, Yoshihisa Hagihara, Yasukazu Yoshida, Aiko Kume, Hiroshi Suzuki
JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION
(2019)