Nanobodies: from high-throughput identification to therapeutic development.

IF 6.1 2区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS Molecular & Cellular Proteomics Pub Date : 2024-10-19 DOI:10.1016/j.mcpro.2024.100865
Peter C Fridy, Michael P Rout, Natalia E Ketaren
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Abstract

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 e.g. 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.

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纳米抗体:从高通量鉴定到治疗开发。
驼科动物单域抗体片段通常被称为纳米抗体,其靶向能力仅为传统单克隆抗体(mAbs)的一小部分。纳米抗体是从驼科动物(包括美洲驼、羊驼和骆驼)身上分离出来的,与传统抗体相比,它的体积小(15 kDa)、结构复杂度低、稳定性高,因此纳米抗体技术成为生物技术发展的焦点。纳米抗体被证明是对传统 mAb 疗法的有力补充,在治疗自身免疫性疾病和癌症等方面取得了成功,最近还成为治疗由快速发展的生物靶标(如 SARS-CoV-2 病毒)引起的传染性疾病的治疗选择。本综述强调了应用蛋白质组学方法识别针对单一抗原的多种纳米抗体序列的好处。这种蛋白质组学方法与传统的酵母/噬菌体展示方法相结合,能生产出高度多样化的纳米抗体,这些抗体能结合抗原的大量表位,其表位采样率超过了 mAbs。此外,我们还将重点介绍纳米抗体的最新研究成果,这些研究成果揭示了纳米抗体的结构特性,这些特性使纳米抗体特别适合于全面的抗原取样和协同活性--强调了获得针对单一抗原的大量、多样化纳米抗体库的强大优势。最后,我们重点介绍了纳米抗体的临床开发工作,纳米抗体作为强大的诊断试剂和治疗方案具有巨大的潜力,尤其是在针对传染病病原体时。
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来源期刊
Molecular & Cellular Proteomics
Molecular & Cellular Proteomics 生物-生化研究方法
CiteScore
11.50
自引率
4.30%
发文量
131
审稿时长
84 days
期刊介绍: The mission of MCP is to foster the development and applications of proteomics in both basic and translational research. MCP will publish manuscripts that report significant new biological or clinical discoveries underpinned by proteomic observations across all kingdoms of life. Manuscripts must define the biological roles played by the proteins investigated or their mechanisms of action. The journal also emphasizes articles that describe innovative new computational methods and technological advancements that will enable future discoveries. Manuscripts describing such approaches do not have to include a solution to a biological problem, but must demonstrate that the technology works as described, is reproducible and is appropriate to uncover yet unknown protein/proteome function or properties using relevant model systems or publicly available data. Scope: -Fundamental studies in biology, including integrative "omics" studies, that provide mechanistic insights -Novel experimental and computational technologies -Proteogenomic data integration and analysis that enable greater understanding of physiology and disease processes -Pathway and network analyses of signaling that focus on the roles of post-translational modifications -Studies of proteome dynamics and quality controls, and their roles in disease -Studies of evolutionary processes effecting proteome dynamics, quality and regulation -Chemical proteomics, including mechanisms of drug action -Proteomics of the immune system and antigen presentation/recognition -Microbiome proteomics, host-microbe and host-pathogen interactions, and their roles in health and disease -Clinical and translational studies of human diseases -Metabolomics to understand functional connections between genes, proteins and phenotypes
期刊最新文献
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