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Mammalian Expression Cassette Engineering For High-Level Protein Production

July 24, 2009

By Dale L. Ludwig

Pharmaceutical and biotechnology company interest in developing biologic therapies has increased dramatically in recent years. The prospect of a blockbuster biologic has been realized with the clinical success of several products including Rituxan, Epogen, and Avastin. Some 16 monoclonal antibodies (MAbs) have been approved for pharmaceutical use, and more than 100 are currently in clinical trials.

Until relatively recently, the major impediment to widespread development of these biologics was their cost of goods: Typical expression levels in mammalian cells, the preferred host, were relatively poor by comparison with other production systems. However, the productive potential of engineered mammalian cell culture expression systems has greatly increased in recent years (1). Recombinant-based production cell lines now boast routine productivity levels in the 1–2 g/L range, and yields of greater than 5 g/L were recently reported by Lonza scientists (www.lonzabiologics.com). Productivity levels in engineered cell lines even 10 years ago was routinely in the range of just a few hundred milligrams per liter.

Reprinted with permission from BioProcess International 4(5):S14-S23 (May 2006)

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