Phage Display - Applications

Applications

Applications of phage display technology include determination of interaction partners of a protein (which would be used as the immobilised phage "bait" with a DNA library consisting of all coding sequences of a cell, tissue or organism) so that the function or the mechanism of the function of that protein may be determined. Phage display is also a widely used method for in vitro protein evolution (also called protein engineering). As such, phage display is a useful tool in drug discovery. It is used for finding new ligands (enzyme inhibitors, receptor agonists and antagonists) to target proteins. The technique is also used to determine tumour antigens (for use in diagnosis and therapeutic targeting) and in searching for protein-DNA interactions using specially-constructed DNA libraries with randomised segments.

The invention of antibody phage display by laboratories at the MRC Laboratory of Molecular Biology led by Greg Winter and John McCafferty and at The Scripps Research Institute led by Richard Lerner and Carlos F. Barbas revolutionised antibody drug discovery. In 1991, The Scripps group reported the first display and selection of human antibodies on phage. This initial study described the rapid isolation of human antibody Fab that bound tetanus toxin and the method was then extended to rapidly clone human anti-HIV-1 antibodies for vaccine design and therapy.

Phage display of antibody libraries has become a powerful method for both studying the immune response as well as a method to rapidly select and evolve human antibodies for therapy. Antibody phage display was later used by Carlos F. Barbas at The Scripps Research Institute to create the first synthetic human antibody libraries, thereby allowing human antibodies to be created in vitro from synthetic diversity elements.

Antibody libraries displaying millions of different antibodies on phage are often used in the pharmaceutical industry to isolate highly specific therapeutic antibody leads, for development into antibody drugs primarily as anti-cancer or anti-inflammatory therapeutics. One of the most successful was HUMIRA (adalimumab), discovered by Cambridge Antibody Technology as D2E7 and developed and marketed by Abbott Laboratories. HUMIRA, an antibody to TNF alpha, was the world's first fully human antibody, which achieved annual sales exceeding $1bn.

Competing methods for in vitro protein evolution are yeast display, bacterial display, ribosome display, and mRNA display.