Patent ID: 7442159

Claim:
A method for the selection of a bacteriophage comprising the steps of: (a) providing a plurality of bacteriophage encoding and displaying a fusion polypeptide, said displayed fusion polypeptide comprising a heterologous polypeptide inserted into the sequence of a bacteriophage coat wherein said plurality of bacteriophage comprise a sequence specific protease cleavable site located within the displayed polypeptide and which site is protected by folding of the displayed fusion polypeptide and is either absent from the bacteriophage other than the site specific insertion, or inaccessible to cleavage, or present only in bacteriophage proteins not required after bacteriophage assembly to mediate infection and wherein cleavage of said sequence specific protease cleavable site impairs infection by a said bacteriophage; (b) exposing the bacteriophage to a protease that recognizes said sequence specific protease cleavable site, wherein said protease only cleaves said sequence specific protease cleavable site if said displayed fusion polypeptide is not properly folded, such that said exposing selects against bacteriophage displaying fusion polypeptide that is not properly folded; and (c) propagating a bacteriophage comprising intact displayed fusion polypeptide.