Phage display is a laboratory platform that allows scientists to study protein interactions on a large-scale and select proteins with the highest affinity for specific targets.
The photograph shows a phage as seen under a microscope. Credit: Ian Hands-Portman.
Connections Laboratory of Molecular Biology
The key advantage of phage display is that it provides a means to identify target-binding proteins from a library of millions of different proteins without the need to screen each molecule individually. This makes it possible to screen billions of proteins each week. By linking a selected protein with its encoding gene, phage display also provides a means to easily identify coding sequences of binding proteins. These can be stored, amplified or processed in other ways. Phage display is a pivotal tool for early basic scientific research and for the development of new drugs and vaccines. The technology has proved particularly important to the production of safer and more effective monoclonal antibody drugs. Phage display libraries consisting entirely of human antibody sequences, for example, have made it possible to produce fully human antibodies. The first fully human therapeutic antibody (adalimumab), a blockbuster drug, generated US$9.3 billion in annual sales in 2012. Four fully human therapeutic antibodies currently approved as treatments in the US and the UK were developed using phage display and many more are in the pipeline. Phage display is also used to develop vaccines for conditions such as prostate cancer and HIV. It is also an important tool for the generation of diagnostic tests for monitoring disease progression and evaluating treatment efficacy.
Phage display was first described by George P Smith in 1985, who deployed it as a method to identify a gene against which he had raised antibodies. The technique was taken further by Greg Winter and John McCafferty at the Laboratory of Molecular Biology in Cambridge, UK, and Richard Lerner and Carlos F. Barbas at The Scripps Research institute, US, who independently used phage display to build large libraries of fully human antibody sequences. This work laid the foundation for the development of human antibody based drugs. Today there are several types of phage display libraries, including peptide libraries, protein libraries and antibody libraries.
Any laboratory that is well versed in basic microbiology can easily make a phage display library with minimum expense. This has allowed phages to become an invaluable tool for basic immunological and cellular biological research as well as for the development of new drugs and vaccines. Prior to the development of phage display, drug development depended on the time-consuming and expensive process of combing through hundreds of thousands of components using tests conducted in test tubes or laboratory dishes.
Phage display: timeline of key events
|1815||Discovery of bacteriophages, type of virus that attacks bacteria, by English bacteriologist William Twort||Twort||University of London|
|18 Dec 1922||Esther Lederberg was born in Bronx, New York, USA||Lederberg||Wisconsin University|
|1940||First electron microscope pictures of bacteriophages published||Ruska|
|1985||Phage display method is developed for selecting peptides, proteins or antibodies from a wide number of variants.||Smith||University of Missouri|
|1989||Cambridge Antibody Technology (CAT) founded||Winter, Chiswell||Laboratory of Molecular Biology, CAT|
|1990||Phage display monoclonal antibodies created||Winter||Laboratory of Molecular Biology, CAT|
|1991||First display and selection of human antibodies phage||Barbas, Lerner||Scripps Research Institute|
|December 2002||First monoclonal antibody made using phage display approved for market||CAT, BASF, Abbott|
|11 Nov 2006||Esther Lederberg died||Lederberg||Wisconsin University|
Discovery of bacteriophages, type of virus that attacks bacteria, by English bacteriologist William Twort
18 Dec 1922
Esther Lederberg was born in Bronx, New York, USA
First electron microscope pictures of bacteriophages published
Phage display method is developed for selecting peptides, proteins or antibodies from a wide number of variants.
Cambridge Antibody Technology (CAT) founded
Phage display monoclonal antibodies created
First display and selection of human antibodies phage
First monoclonal antibody made using phage display approved for market
11 Nov 2006
Esther Lederberg died