On the origin of non-specific binders isolated in the selection of phage display peptide libraries

Over the recent decades, phage display has been used successfully to identify a variety of peptides with diagnostic and therapeutic applications. Despite the significant role of this technology in the pharmaceutical industry, the affinity selection of phage display peptide libraries through biopanni...

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Main Authors: Babak Bakhshinejad, Andreas Kjaer
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Microbiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fmicb.2025.1571679/full
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author Babak Bakhshinejad
Babak Bakhshinejad
Andreas Kjaer
Andreas Kjaer
author_facet Babak Bakhshinejad
Babak Bakhshinejad
Andreas Kjaer
Andreas Kjaer
author_sort Babak Bakhshinejad
collection DOAJ
description Over the recent decades, phage display has been used successfully to identify a variety of peptides with diagnostic and therapeutic applications. Despite the significant role of this technology in the pharmaceutical industry, the affinity selection of phage display peptide libraries through biopanning suffers from some limitations. The most significant drawback of phage display is the undesirable enrichment and isolation of phages whose displayed peptides have no binding affinity toward the target. Phages with high amplification rates constitute the most important category of non-specific binders. Amplification, which aims to increase the copy number of phages displaying target-specific peptides, acts like a double-edged blade and can also make a major contribution to the target-unrelated enrichment of non-specific binders, leading to compositional bias in the sequence content of the biopanning output. The cutting-edge breakthroughs fueled by the integration of next-generation sequencing (NGS) into phage display have led researchers to gain a deeper understanding of the information content of the phage population recovered from biopanning and how its peptide content changes during further rounds of selection and amplification. This body of vastly increasing information has shed more light on the complications encountered during library selection and opened new perspectives to obtain in-depth insights into amplification-associated bias in the selected phage display libraries, analyze biopanning data more rigorously, and devise more optimal protocols for phage display selections. This knowledge can finally provide a solid foundation for discovering promising target-specific binders in the evolutionary selection of phage display libraries.
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spelling doaj-art-28a718bd598e4a45a13fe31389f39dd22025-08-20T03:20:10ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2025-06-011610.3389/fmicb.2025.15716791571679On the origin of non-specific binders isolated in the selection of phage display peptide librariesBabak Bakhshinejad0Babak Bakhshinejad1Andreas Kjaer2Andreas Kjaer3Cluster for Molecular Imaging, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, DenmarkDepartment of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital-Rigshospitalet, Copenhagen, DenmarkCluster for Molecular Imaging, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, DenmarkDepartment of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital-Rigshospitalet, Copenhagen, DenmarkOver the recent decades, phage display has been used successfully to identify a variety of peptides with diagnostic and therapeutic applications. Despite the significant role of this technology in the pharmaceutical industry, the affinity selection of phage display peptide libraries through biopanning suffers from some limitations. The most significant drawback of phage display is the undesirable enrichment and isolation of phages whose displayed peptides have no binding affinity toward the target. Phages with high amplification rates constitute the most important category of non-specific binders. Amplification, which aims to increase the copy number of phages displaying target-specific peptides, acts like a double-edged blade and can also make a major contribution to the target-unrelated enrichment of non-specific binders, leading to compositional bias in the sequence content of the biopanning output. The cutting-edge breakthroughs fueled by the integration of next-generation sequencing (NGS) into phage display have led researchers to gain a deeper understanding of the information content of the phage population recovered from biopanning and how its peptide content changes during further rounds of selection and amplification. This body of vastly increasing information has shed more light on the complications encountered during library selection and opened new perspectives to obtain in-depth insights into amplification-associated bias in the selected phage display libraries, analyze biopanning data more rigorously, and devise more optimal protocols for phage display selections. This knowledge can finally provide a solid foundation for discovering promising target-specific binders in the evolutionary selection of phage display libraries.https://www.frontiersin.org/articles/10.3389/fmicb.2025.1571679/fullamplificationbiopanning outputcompositional biasnext-generation sequencingnon-specific binderpeptide library
spellingShingle Babak Bakhshinejad
Babak Bakhshinejad
Andreas Kjaer
Andreas Kjaer
On the origin of non-specific binders isolated in the selection of phage display peptide libraries
Frontiers in Microbiology
amplification
biopanning output
compositional bias
next-generation sequencing
non-specific binder
peptide library
title On the origin of non-specific binders isolated in the selection of phage display peptide libraries
title_full On the origin of non-specific binders isolated in the selection of phage display peptide libraries
title_fullStr On the origin of non-specific binders isolated in the selection of phage display peptide libraries
title_full_unstemmed On the origin of non-specific binders isolated in the selection of phage display peptide libraries
title_short On the origin of non-specific binders isolated in the selection of phage display peptide libraries
title_sort on the origin of non specific binders isolated in the selection of phage display peptide libraries
topic amplification
biopanning output
compositional bias
next-generation sequencing
non-specific binder
peptide library
url https://www.frontiersin.org/articles/10.3389/fmicb.2025.1571679/full
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