Methods for optimizing assembly and production of heteromultimeric protein complexes

摘要

A method is provided for improving the expression of a protein complex by adjusting the expression level of each component required for assembly of the complex. These methods are effective in limiting the expression of the dominant strands and thus balancing their relative abundance. The methods provided herein result in significant increases in productivity and final bispecific yield in both stably transfected mammalian cells in addition to the transient expression system. In contrast to previously described approaches, reducing the expression of one or several polypeptides in a protein complex enhances the assembly and yield of the protein complex.