Phages from landscape libraries as substitute antibodies.

Abstract

In 'landscape' phage, as in traditional phage-display constructs, foreign peptides or proteins are fused to coat proteins on the surface of a filamentous phage particle. Unlike conventional constructs, however, each virion displays thousands of copies of the peptide in a repeating pattern, subtending a major fraction of the viral surface. The phage body serves as an interacting scaffold to constrain the peptide into a particular conformation, creating a defined organic surface structure ('landscape') that varies from one phage clone to the next. By testing landscape libraries with three representative antigens (streptavidin from the bacterium Streptomyces avidinii, avidin from chicken egg white and beta-galactosidase from Escherichia coli) we have shown that landscape phages may be used as a new type of substitute antibodies-filaments that can bind protein and glycoprotein antigens with nanomolar affinities and high specificity. In many ways these substitute antibodies are more convenient than their natural immunoglobulin counterparts.