Method for producing protein libraries and for selecting proteins from said libraries

A method of producing a library of antibody-producing eukaryotic cells, the method comprising the steps of:

• (a) introducing specific FRT recombination signals into at least one chromosomal gene locus of a eukaryotic cell;
• (b) expanding the eukaryotic cell comprising the specific FRT recombination signals in the at least one gene locus;
• (c) introducing into the expanded eukaryotic cells of step (b) a plurality of nucleic acids comprising homologous sequences and encoding a plurality of antibodies;
• (d) introducing into the expanded eukaryotic cells of step (b) a nucleic acid encoding a Flp recombinase recognizing the specific FRT recombination signals;
• and
• (e) selecting eukaryotic cells expressing said plurality of antibodies,
• wherein the plurality of nucleic acids replace the at least one gene locus of the expanded eukaryotic cells,
• wherein a library of more than 102 different antibody-producing eukaryotic cells is produced, and
• wherein members of the library of antibody-producing eukaryotic cells express an antibody encoded by the plurality of nucleic acids and bound to the surface of the members of the library of antibody-producing eukaryotic cells, wherein said antibody-producing eukaryotic cells are mammalian cells or hybridoma cells.