Applications of Phage Display

Sharon Craggs

Nov 19, 2019

Phage display is a rapidly evolving technology that has been used to support a range of applications. Depending on the nature of the phage display library, these include epitope mapping, receptor and ligand identification, protein-protein interaction studies, recombinant antibody production, directed evolution of proteins, and drug discovery. The widespread utility of this technology is backed by a growing number of citations, highlighting its importance to accelerate research.

Epitope Mapping

When an antibody recognises a specific antigen, the region of the antigen to which it binds is referred to as the epitope. Knowledge of antigenic epitopes is valuable for the development of effective antibody reagents, either for research use or as therapeutics, and can help researchers to elucidate immune responses. Epitope mapping also has significant utility in vaccine development, for example enabling the construction of peptide vaccines which are based on specific epitopes. Using phage display to present large numbers of peptides to an antibody, it is possible to gain detailed insight regarding antibody binding to its target.

Receptor and Ligand Identification

Phage display is an efficient method to determine which proteins or peptides bind specifically to predefined targets. This facilitates the study of receptor-ligand interactions, shedding new light on cellular signalling pathways through the identification of key inhibitors, agonists and antagonists. In situations where a receptor interacts with multiple ligands, this technology can help to classify those ligands with the highest binding affinity, thereby directing further downstream research.

Protein-Protein Interaction Studies

Virtually all biological processes are mediated by protein-protein interactions. By providing a means of evaluating complex inter-protein relationships, phage display allows researchers to identify known and novel protein binding partners and to evaluate the specificity of these associations. As just one example, the use of phage display to present multiple phosphorylated and unmodified peptides to a target protein can inform the phospho-specificity of a protein-protein interaction.

Recombinant Antibody Production

Antibody phage display is regarded by many as the gold standard in recombinant antibody production. By screening large numbers of antibody-displaying phage against a target antigen, researchers can quickly identify phage which express an antibody specific for the target. One method of producing a library of antibody-displaying phage is to immunise an animal, isolate B-cells, extract mRNA and synthesise cDNA encoding antibody single-chain variable regions (scFv) for cloning into phagemid vectors. It is also possible to purchase pre-synthesised libraries consisting of many different antibody scFv genes.

Directed Evolution of Proteins

Directed evolution introduces desirable features into an existing protein, typically through the acquisition of mutations. This can result in altered specificity for a binding partner or may change the properties or function of the protein in comparison to the original biomolecule. Using a phage display library composed of multiple protein variants, researchers can identify those mutations which contribute to required characteristics.

Drug Discovery

Phage display has widespread utility within drug discovery. It can facilitate the identification of peptide ligands for therapeutic targets, providing a launch point for drug discovery efforts, and it is also pivotal to understand how these biomolecules may cross-react with other proteins. Research groups focussed on developing antibody drugs use phage display to investigate antibody selectivity, while the technology can also be employed to identify scFv fragments suitable for targeted delivery of cytotoxic agents to tumours.

To successfully integrate this technology into a new or existing workflow, it can be sensible to seek the advice of an experienced provider of phage display services. Offering comprehensive expertise in multiple phage display applications, a trusted partner can deliver high-quality phage display services to meet a range of exacting requirements. At Pivotal Scientific, we’re well placed to introduce you to experts in phage display, whatever your research requirements.

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