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RNA interference of cofilin in Chinese hamster ovary cells improves recombinant protein productivity

Authors

  • Stephanie Hammond,

    1. Department of Chemical Engineering and Delaware Biotechnology Institute, University of Delaware, Newark, Delaware 19711; telephone: 302-831-0344; fax: 302-831-4841
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  • Kelvin H. Lee

    Corresponding author
    1. Department of Chemical Engineering and Delaware Biotechnology Institute, University of Delaware, Newark, Delaware 19711; telephone: 302-831-0344; fax: 302-831-4841
    • Department of Chemical Engineering and Delaware Biotechnology Institute, University of Delaware, Newark, Delaware 19711; telephone: 302-831-0344; fax: 302-831-4841.
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Abstract

RNA interference (RNAi) has been recently applied to improve the yield and quality of recombinant proteins produced in Chinese hamster ovary (CHO) cells, the most commonly used mammalian cell line for production of complex biopharmaceuticals. Proteomic profiling of CHO cells undergoing gene amplification identified cofilin, a key regulatory protein of actin cytoskeletal dynamics, as a cellular target for genetic engineering studies. Transient reduction of cofilin by small interfering RNA (siRNA) enhanced specific productivity in recombinant CHO cells by up to 80%. CHO cell lines expressing cofilin-specific short hairpin RNA (shRNA) vectors showed up to a 65% increase in specific productivity. These results suggest that modulation of cofilin, and its regulatory pathways, may be a new approach to enhance recombinant protein productivity in CHO cells. Biotechnol. Bioeng. 2012; 109:528–535. © 2011 Wiley Periodicals, Inc.

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