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Enhancing Recombinant Protein Production Processes

High Value, Low Cost of Goods

The market demand for recombinant proteins as therapeutics remains strong in recent years. The higher dosage requirement for antibody drugs has driven the need for efficient, high-titer recombinant protein production processes which can dramatically reduce the cost of goods during manufacturing.

To accomplish this, A*STAR’s Bioprocessing Technology Institute (BTI) has developed chemically defined protein-free media and optimized feeding strategies for recombinant therapeutic protein production in Chinese Hamster Ovary (CHO) and other mammalian cell lines. Using new technologies such as Metabolomics, intra- and extra-cellular metabolites are tracked in high density cultures to guide media design for improved culture performance. In addition, a technique to control gene expression for antibody production is established by mutating the polyadenylation signal. Microarray and proteomic analyses of high density fed-batch cultures has also led to the identification of targets for cell engineering and the generation of anti-apoptotic CHO Gene-Targeted (GT) cell lines with extended viabilities and increased recombinant protein production titers.

These technologies contribute to the state-of-the-art in recombinant protein manufacturing by improving the production processes of these high value therapeutics. With these capabilities, BTI has also attracted collaborators from the biopharmaceutical industry, including GlaxoSmithKline and Genentech.

References

  • Yang Y, Mariati, Ho SCL, Yap MGS
    Mutated Polyadenylation Signals for Controlling Expression Levels of Multiple Genes in Mammalian Cells
    Biotechnology and Bioengineering 102: 1152-1160, 2009.
  • Lee YY, Wong TKK, Nissom PM, Wong DCF, Yap MGS
    Transcriptional profiling of batch and fed-batch protein-free 293-HEK cultures.
    Metabolic Engineering 9(1): 52-67, 2007.
  • Wong CFD, Wong TKK, Lee YY, Heng CK, Nissom PM, Yap MGS
    Transcriptional profiling of apoptotic pathways in batch and fed-batch CHO cell cultures.
    Biotechnology and Bioengineering 94(2): 373-382, 2006
  • Wong CFD, Wong TKK, Heng CK, and Yap MGS
    Targeting early apoptotic genes in batch and fed-batch CHO cells cultures.
    Biotechnology and Bioengineering 95(3): 350-361, 2006.

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Last Updated on 27 September 2009

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