Abstract
Arresting cell growth and thus decreasing cell division potentially lessens the chance for genetic drift in the cell population: this would be of utmost importance for the consistent production of high quality products. Cell growth arrest of two industrially relevant animal cell lines (CHO and BHK cells) has been successfully achieved by the overexpression of a cyclin-dependent kinase inhibitor (p27) and of a tumor suppressor gene (IRF-1) (genetic strategy), purines addition (chemical strategy) and by the depletion of essential nutrients from the culture medium (environmental strategy). Adenosine and AMP addition, as well as the overexpression of p27 led to a 3 to 4-fold increase in the specific productivity of two recombinant proteins: the secreted form of the human placental alkaline phosphatase (SEAP) and the coagulation Factor VII. AMP addition showed to be the most promising tool for biopharmaceuticals production: fine tuning of drug addition was required. All the tested cell growth al-rest strategies interfered not only with cell cycle but also with cell metabolism. A careful look onto cell cycle distribution in the different scenarios created, shows whether it is important to consider recombinant protein expression dependency upon cell cycle in process optimization and operation strategies.
Published Version
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