Compositions and method for increasing production of recombinant gamma-carboxylated proteins

A method for the increased production of gamma-carboxylated proteins of interest comprising:

• a) providing a cell line which has been recombinantly engineered to overexpresses VKORC1 and an agent which down regulates the expression of calumenin in said cells, and;
• b) introducing a nucleic acid encoding the gamma-carboxylated protein of interest into the cells of step a) under conditions wherein protein encoded by said nucleic acid is produced.

A cell line for the elevated production of gamma-carboxylated proteins, comprising a vector expressing VKORC1, and a nucleic acid encoding a gamma-carboxylated protein of interest, and optionally, calumenin specific siRNA molecules or calumenin specific antisense oligonucleotides said cell line producing increased levels of said gamma-carboxylated protein relative to cell lines which do not overexpress VKORC1 and calumenin siRNA when present.

The cell line of claim 16, wherein said protein is selected from the group consisting of protein C, protein S, protein Z, GAS6, PRGP1, PRGP2, TmG3, TmG4, osteocalsin, and matrix Gla protein (MGP).