Omidfar Kobra, Daneshpour Maryam
Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Biosensor Research Center , Tehran , Iran
Expert Opin Drug Discov. 2015 Jun;10(6):651-69. doi: 10.1517/17460441.2015.1037738. Epub 2015 Apr 24.
Over the past decade, several library-based methods have been developed to discover ligands with strong binding affinities for their targets. These methods mimic the natural evolution for screening and identifying ligand-target interactions with specific functional properties. Phage display technology is a well-established method that has been applied to many technological challenges including novel drug discovery.
This review describes the recent advances in the use of phage display technology for discovering novel bioactive compounds. Furthermore, it discusses the application of this technology to produce proteins and peptides as well as minimize the use of antibodies, such as antigen-binding fragment, single-chain fragment variable or single-domain antibody fragments like VHHs.
Advances in screening, manufacturing and humanization technologies demonstrate that phage display derived products can play a significant role in the diagnosis and treatment of disease. The effects of this technology are inevitable in the development pipeline for bringing therapeutics into the market, and this number is expected to rise significantly in the future as new advances continue to take place in display methods. Furthermore, a widespread application of this methodology is predicted in different medical technological areas, including biosensing, monitoring, molecular imaging, gene therapy, vaccine development and nanotechnology.
在过去十年中,已经开发了几种基于文库的方法来发现与其靶标具有强结合亲和力的配体。这些方法模拟自然进化以筛选和鉴定具有特定功能特性的配体 - 靶标相互作用。噬菌体展示技术是一种成熟的方法,已应用于许多技术挑战,包括新型药物发现。
本综述描述了噬菌体展示技术在发现新型生物活性化合物方面的最新进展。此外,还讨论了该技术在生产蛋白质和肽以及减少抗体使用方面的应用,例如抗原结合片段、单链可变片段或单域抗体片段(如VHHs)。
筛选、制造和人源化技术的进展表明,噬菌体展示衍生产品可在疾病的诊断和治疗中发挥重要作用。该技术在将治疗药物推向市场的研发流程中的影响是不可避免的,并且随着展示方法不断取得新进展,预计这一数字未来将大幅上升。此外,预计该方法将在不同的医学技术领域得到广泛应用,包括生物传感、监测、分子成像、基因治疗、疫苗开发和纳米技术。