Next Generation, High-Throughput Phage Display - Isis Project No 1506

The technology is the next generation of phage display, allowing the complete molecular diversity in a phage library to be assessed at each selection round and has potential for a multitude of different applications.

Background

Phage display is a very powerful method of probing protein-protein interactions by expressing a vast array of unique polypeptide-based chemical entities on the tip of bacteriophage (viruses that infect bacteria). Phage that bind a specific target can be enriched from non-specific phage by immobilising the target and employing a "bio-panning" procedure. The ability to probe this vast chemical space to select high affinity ligands against novel and existing target classes is well established. The technology is an integral part of biomedical research and drug discovery, but has not been embraced by other sectors.

Opportunity

Although a very powerful technique, phage display does have its limitations. The outcome of repeated rounds of bio-panning from a large peptide phage library (~>109 different phage) is a reduced complexity sub-library (~103-104 different phage) showing affinity for the target. However, the outcome of bio-panning is usually assessed by sequence analysis of a very small sample of the enriched phage population (<20 independent clones) as sequence analysis is both time consuming and cost intensive.

The Oxford Invention

Researchers from The University of Oxford have devised a simple, non-biased, and economical way of sequencing the relevant variable parts of the gene encoding the phage coat protein from a large number (preferably all) of the phage in the selected sub-library, instead of a tiny and potentially unrepresentative subset. This ensures that target-specific phage are identified after each round of bio-panning allowing phage to be tracked through the process. This method overcomes the problems of clonal dominance, which prevents analysis of interactions on complex matrices (e.g. whole cells, implants etc.), and reduces costs significantly.

Patent Status

Isis Innovation has filed a patent application on this technology and is now seeking a commercial partner interested in pursuing this exciting development in the numerous applications available.

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