siRNA silencing of calumenin enhances functional factor IX production

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Abstract
To improve production of functional fully γ-carboxylated recombinant human clotting factor IX (r-hFIX), cell lines stably overexpressing r-hFIX have been engineered to also overexpress proteins of the γ-carboxylation system. Here we demonstrate that siRNA silencing of calumenin, an inhibitor of the γ-carboxylation system, enhances production of functional r-hFIX produced by engineered BHK21 cells. The production yield of functional r-hFIX was 80% in engineered cells where calumenin had been silenced 78%. We propose that this high-yield expression system can easily be adapted to overproduce functional forms of all members of the vitamin K–dependent protein family.