Independent Consultant, UK.
Twist Bioscience, South San Francisco, USA.
Expert Opin Drug Discov. 2024 Aug;19(8):887-915. doi: 10.1080/17460441.2024.2367023. Epub 2024 Jun 18.
Phage display technology is a well-established versatile display technology that has been used for over 35 years to identify peptides and antibodies for use as reagents and therapeutics, as well as exploring the diversity of alternative scaffolds as another option to conventional therapeutic antibody discovery. Such successes have been responsible for spawning a range of biotechnology companies, as well as many complementary technologies devised to expedite the drug discovery process and resolve bottlenecks in the discovery workflow.
In this perspective, the authors summarize the application of phage display for drug discovery and provide examples of protein-based drugs that have either been approved or are being developed in the clinic. The amenability of phage display to generate functional protein molecules to challenging targets and recent developments of strategies and techniques designed to harness the power of sampling diverse repertoires are highlighted.
Phage display is now routinely combined with cutting-edge technologies to deep-mine antibody-based repertoires, peptide, or alternative scaffold libraries generating a wealth of data that can be leveraged, e.g. via artificial intelligence, to enable the potential for clinical success in the discovery and development of protein-based therapeutics.
噬菌体展示技术是一种成熟的多功能展示技术,已经使用了 35 多年,用于鉴定肽和抗体作为试剂和治疗药物,以及探索替代支架的多样性,作为传统治疗性抗体发现的另一种选择。这些成功促使了一系列生物技术公司的诞生,以及许多旨在加速药物发现过程和解决发现工作流程瓶颈的互补技术的出现。
在这篇观点文章中,作者总结了噬菌体展示在药物发现中的应用,并提供了已经批准或正在临床开发的基于蛋白质的药物的实例。噬菌体展示技术生成针对挑战性靶标的功能蛋白分子的适用性,以及设计用于利用多样化库的强大功能的策略和技术的最新进展,都得到了强调。
噬菌体展示现在通常与前沿技术结合使用,以深入挖掘基于抗体、肽或替代支架的文库,生成大量可利用的数据,例如通过人工智能,从而有可能在发现和开发基于蛋白质的治疗药物方面取得临床成功。