Design of synthetic antibody libraries

Antibody libraries came into existence 15 years ago when the accumulating sequence data of immunoglobulin genes and the advent of polymerase chain reaction technology made it possible to clone antibody gene repertoires. Since then, virtually hundreds of antibody libraries have been constructed, employing limitless maneuvers from the antibody engineering molecular bag of tricks towards the crucial parameters that determine library quality, library size, diversity and robustness. Phage and additional display and screening technologies were applied to pan out desired binding specificities from antibody libraries. Several biotech companies established themselves as key operators in the multibillion-dollar field of recombinant antibody technology. Out of nineteen FDA-approved therapeutic antibodies, one was isolated from an antibody library and many more are in various stages of clinical evaluation. This review highlights key milestones in the short history of antibody libraries and attempts to predict the future impact of antibody libraries on drug discovery.