Nanobodies: From High-Throughput Identification to Therapeutic Development.
| Autor: | Fridy PC; Laboratory of Cellular and Structural Biology, The Rockefeller University, New York, New York, USA., Rout MP; Laboratory of Cellular and Structural Biology, The Rockefeller University, New York, New York, USA., Ketaren NE; Laboratory of Cellular and Structural Biology, The Rockefeller University, New York, New York, USA. Electronic address: nketaren@rockefeller.edu. |
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| Jazyk: | angličtina |
| Zdroj: | Molecular & cellular proteomics : MCP [Mol Cell Proteomics] 2024 Oct 19; Vol. 23 (12), pp. 100865. Date of Electronic Publication: 2024 Oct 19. |
| DOI: | 10.1016/j.mcpro.2024.100865 |
| Abstrakt: | The camelid single-domain antibody fragment, commonly referred to as a nanobody, achieves the targeting power of conventional monoclonal antibodies (mAbs) at only a fraction of their size. Isolated from camelid species (including llamas, alpacas, and camels), their small size at ∼15 kDa, low structural complexity, and high stability compared with conventional antibodies have propelled nanobody technology into the limelight of biologic development. Nanobodies are proving themselves to be a potent complement to traditional mAb therapies, showing success in the treatment of, for example, autoimmune diseases and cancer, and more recently as therapeutic options to treat infectious diseases caused by rapidly evolving biological targets such as the SARS-CoV-2 virus. This review highlights the benefits of applying a proteomic approach to identify diverse nanobody sequences against a single antigen. This proteomic approach coupled with conventional yeast/phage display methods enables the production of highly diverse repertoires of nanobodies able to bind the vast epitope landscape of an antigen, with epitope sampling surpassing that of mAbs. Additionally, we aim to highlight recent findings illuminating the structural attributes of nanobodies that make them particularly amenable to comprehensive antigen sampling and to synergistic activity-underscoring the powerful advantage of acquiring a large, diverse nanobody repertoire against a single antigen. Lastly, we highlight the efforts being made in the clinical development of nanobodies, which have great potential as powerful diagnostic reagents and treatment options, especially when targeting infectious disease agents. Competing Interests: Conflict of interests The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.) |
| Databáze: | MEDLINE |
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