Construction and Use of Large Antibody Libraries in Mammalian Cells
John McCafferty,
Founder & CEO,
IONTAS Ltd
Display technologies such as phage display have permitted the ready isolation of novel binding molecules from very large libraries. Creation of large libraries of antibodies within mammalian cells would allow expression in an IgG format and enable flow sorting of cell clones on the basis of expression level and affinity of the desired format within the cell types typically used for production. In addition functional screening could be carried out directly within a cell type of interest. The main limitation to achieving large libraries in mammalian cells has been the inability to construct sufficiently large libraries containing a single binder gene/cell. We have solved this problem by directing the integration of antibody genes into a single genomic locus through the use of site-specific nucleases. Antibody libraries consisting of many millions of clones have been constructed and binders selected. We have also demonstrated the potential of this approach for the isolation and engineering of T cell receptors.
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