METHOD FOR OPTIMIZING THE ASSEMBLY AND PRODUCTION OF HETERO-MULTIMERIC PROTEIN COMPLEXES

摘要

Methods are provided to improve the expression of protein complexes by tuning the expression levels of each component required for the assembly of the complex. These methods are effective in limiting the expression of the dominant chain and, thus, equilibrating their relative abundance. The methods provided herein lead to a significant increase in productivity and final bispecific yields both in transient expression systems as well as in stably transfected mammalian cells.

主权项

1. A method to increase production yield of a protein complex that comprises more than one polypeptide, the method comprising:
(a) providing one or more nucleic acid molecules encoding the polypeptides in the protein complex; (b) introducing the nucleic acid molecule(s) into a cell; (c) culturing the cell under conditions that allow for the expression of polypeptides in the protein complex; and (d) decreasing expression of at least one of the polypeptides in the protein complex.