Multivariate Optimization of the Refolding Process of an Incorrectly Folded Fc-Fusion Protein in a Cell Culture Broth.

Background: Protein misfolding is a common problem in large-scale production of recombinant proteins, which can significantly reduce the yield of the process.

Objective: In this work, we aimed at treating a cell culture broth containing high levels (>45%) of incorrectly folded Fc-fusion proteins by a simple redox buffer system in order to increase the proportion of the protein with correct conformation.

Methods: Multi-variable process optimization was firstly conducted at a small scale (25 mL), employing an experimental design methodology.