Biomedical Engineering Reference
In-Depth Information
nutritional requirement, grow more slowly and are far more susceptible to physical damage. In
industrial terms, this translates into increased production costs.
In addition to recombinant biopharmaceuticals, animal cell culture is used to produce various
other biologically based pharmaceuticals. Chief amongst these are a variety of vaccines and hy-
bridoma cell-produced monoclonal antibodies (Chapter 13). Earlier interferon preparations were
also produced in culture by a particular lymphoblastoid cell line (the Namalwa cell line), which
was found to synthesize high levels of several IFN-
α
's naturally (Chapter 8).
5.2.3 Additional production systems
5.2.3.1 Yeast
Attention has also focused upon a variety of additional production systems for recombinant biop-
harmaceuticals. Yeast cells (particularly
Saccharomyces cerevisiae
) display a number of charac-
teristics that make them attractive in this regard. These characteristics include:
•
their molecular biology has been studied in detail, facilitating their genetic manipulation;
•
most are GRAS-listed organisms ('generally regarded as safe'), and they have a long history of
industrial application (e.g. in brewing and baking);
•
they grow relatively quickly in relatively inexpensive media, and their tough outer wall protects
them from physical damage;
•
suitable industrial-scale fermentation equipment/technology is already available;
•
they possess the ability to carry out post-translational modifi cations of proteins.
The practical potential of yeast-based production systems has been confi rmed by the successful ex-
pression of a whole range of proteins of therapeutic interest in such systems. However, a number of
disadvantages relating to heterologous protein production in yeast have been recognized. These include:
•
Although capable of glycosylating heterologous human proteins, the glycosylation pattern usu-
ally varies from the pattern observed on the native glycoprotein (when isolated from its natural
source, or when expressed in recombinant animal cell culture systems).
•
In most instances, expression levels of heterologous proteins remain less than 5 per cent of total
cellular protein. This is signifi cantly lower than expression levels typically achieved in recom-
binant
E. coli
systems.
Despite such potential disadvantages, several recombinant biopharmaceuticals now ap-
proved for general medical use are produced in yeast (
S. cerevisiae
)-based systems (Table
5.5). Interestingly, most such products are not glycosylated. The oligosaccharide component of
glycoproteins produced in yeasts generally contains high levels of mannose. Such high mannose-
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