Advanced applications of Nanodiscs-based platforms for antibodies discovery

IF 3.3 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Biophysical chemistry Pub Date : 2024-07-10 DOI:10.1016/j.bpc.2024.107290
Kristina O. Baskakova , Pavel K. Kuzmichev , Mikhail S. Karbyshev
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Abstract

Due to their fundamental biological importance, membrane proteins (MPs) are attractive targets for drug discovery, with cell surface receptors, transporters, ion channels, and membrane-bound enzymes being of particular interest. However, due to numerous challenges, these proteins present underutilized opportunities for discovering biotherapeutics. Antibodies hold the promise of exquisite specificity and adaptability, making them the ideal candidates for targeting complex membrane proteins. They can target specific conformations of a particular membrane protein and can be engineered into various formats. Generating specific and effective antibodies targeting these proteins is no easy task due to several factors. The antigen's design, antibody-generation strategies, lead optimization technologies, and antibody modalities can be modified to tackle these challenges. The rational employment of cutting-edge lipid nanoparticle systems for retrieving the membrane antigen has been successfully implemented to simplify the mechanism-based therapeutic antibody discovery approach. Despite the highlighted MP production challenges, this review unequivocally underscores the advantages of targeting complex membrane proteins with antibodies and designing membrane protein antigens. Selected examples of lipid nanoparticle success have been illustrated, emphasizing the potential of therapeutic antibody discovery in this regard. With further research and development, we can overcome these challenges and unlock the full potential of therapeutic antibodies directed to target complex MPs.

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基于纳米盘的抗体发现平台的高级应用。
膜蛋白(MPs)具有重要的生物学基础,是极具吸引力的药物发现目标,其中细胞表面受体、转运体、离子通道和膜结合酶尤其令人感兴趣。然而,由于面临诸多挑战,这些蛋白质在发现生物治疗药物方面的机会尚未得到充分利用。抗体具有良好的特异性和适应性,是靶向复杂膜蛋白的理想候选物。它们可以靶向特定膜蛋白的特定构象,并可被设计成各种形式。由于多种因素的影响,要产生针对这些蛋白质的特异而有效的抗体并非易事。抗原设计、抗体生成策略、先导优化技术和抗体模式都可以通过改进来应对这些挑战。合理利用最先进的脂质纳米粒子系统来回收膜抗原,简化了基于机制的治疗性抗体发现方法,已获得成功。尽管纳米脂质颗粒的生产面临诸多挑战,本综述仍明确强调了用抗体靶向复杂膜蛋白和设计膜蛋白抗原的优势。本文列举了一些脂质纳米粒子的成功实例,强调了治疗性抗体发现在这方面的潜力。通过进一步的研究和开发,我们可以克服这些挑战,充分释放针对复杂膜蛋白的治疗性抗体的潜力。
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来源期刊
Biophysical chemistry
Biophysical chemistry 生物-生化与分子生物学
CiteScore
6.10
自引率
10.50%
发文量
121
审稿时长
20 days
期刊介绍: Biophysical Chemistry publishes original work and reviews in the areas of chemistry and physics directly impacting biological phenomena. Quantitative analysis of the properties of biological macromolecules, biologically active molecules, macromolecular assemblies and cell components in terms of kinetics, thermodynamics, spatio-temporal organization, NMR and X-ray structural biology, as well as single-molecule detection represent a major focus of the journal. Theoretical and computational treatments of biomacromolecular systems, macromolecular interactions, regulatory control and systems biology are also of interest to the journal.
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