期刊
BIOTECHNOLOGY PROGRESS
卷 27, 期 5, 页码 1273-1281出版社
WILEY
DOI: 10.1002/btpr.642
关键词
protein refolding; high-pressure technology; angiogenesis; biomanufacturing; homodimer
High-pressure has been established as an effective technique for refolding proteins at high concentrations. In this study, high hydrostatic pressure (1-3 kbar) was utilized to refold a homodimeric protein from inclusion bodies and the process was evaluated for large-scale manufacturing feasibility. This research focused on increasing protein concentration while maximizing yield and product quality. Refolding yields of 29-42% were achieved in the absence of urea at 2 kbar and at a protein concentration of 6 g/L. Optimization of the refolding buffer composition via multivariate design of experiments and other process parameters such as refolding pressure, gas sparging, and time under pressure are discussed. Although high-pressure refolding can be considered a viable technology for manufacturing if the gains are clearly identified, in this particular case, the benefits that the high-pressure technology offers do not compensate for the drawbacks of implementing new equipment in an existing facility, and unknown impact of scale-up for this molecule. (C) 2011 American Institute of Chemical Engineers Biotechnol. Prog., 27: 1273-1281, 2011
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