Applications of Phage Display

Sharon Craggs

Sep 24, 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 phage display 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, phage display 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 phage
display 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. Contact us to find out more.

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