Patent ID: 6420110
Filing Date: 2002-07-16
Classification: A61P,C12N,C40B

Abstract:
A method for identifying a peptide with a selected biological activity, comprising the steps of:(i) providing a peptide display library comprising a variegated population of test peptides expressed on the surface of a population of display packages each of the test peptide being encoded by a chimeric gene; (ii) isolating, in a display mode, from the peptide display library, a sub-population of display packages enriched for test peptides which have a desired binding specificity or affinity for a cell or a cell component, (iii) expressing, in a secretion mode, chimeric gene associated with the subpopulation of display packages in eukaryotic cells under conditions wherein the test peptides are secreted and are free of the display packages; and (iv) assessing the ability of the secreted test peptides to regulate a biological process in a target cell, thereby identifying peptides with a selected biological activity, wherein each chimeric gene comprises (i) a coding sequence for the test peptide, (ii) a coding sequence for a surface protein of the display package for displaying the test peptides on the surface of a population of display packages, and (iii) RNA splice sites flanking the coding sequence for the surface protein, wherein, in the display mode, the chimeric gene is expressed as fusion protein including the test peptide and the surface protein, whereas in the secretion mode, the test peptide is expressed without the surface protein as a result of the coding sequence for the surface protein being removed by RNA splicing, andwherein the chimeric gene is included in a vector which further includes an origin of replication for a prokaryotic cell, a transcriptional regulatory element for expressing the chimeric gene in a prokaryotic cell, a transcriptional regulatory element for expressing the chimeric gene in a eukaryotic cell, a secretion signal, a coding sequence for a phage coat protein, a marker gene, and a phage origin of replication.