Use of MAR Elements to Increase the Production of Recombinant Proteins

  • Cori Gorman
  • Salina Arope
  • Mélanie Grandjean
  • Pierre-Alain Girod
  • Nicolas MermodEmail author
Part of the Cell Engineering book series (CEEN, volume 6)


The biopharmaceutical industry continues to face the challenge of producing large amount of recombinant proteins for use as therapeutics, and eighty percent of protein therapeutics in clinical development are produced in mammalian cell systems. Approaches to increase production addressing growth conditions, such as the improvement of media composition and process control, or transcription of the recombinant gene via the use of strong promoters/enhancers and amplification of gene copy number, have increased the yields obtained from mammalian cells considerably over the past decades. However these processes remain laborious, and extensive screening of clones is often required, as stable cell line and/or protein production is not always obtained. Unstable or variable expression is linked to the location of transgene integration site, the regulation of gene expression, the silencing of genes, and the loss of gene copies. Genetic elements that may remodel chromatin to maintain the transgene in an active configuration are now being employed increasingly to improve protein production using mammalian cells. Here we will review how one type of such elements, the MARs, may increase transgene integration into the cell genome and decrease silencing effects to reduce expression variability. We also illustrate how inclusion of these elements in expression vectors leads to increased specific productivities ranging from 20 to 100 picograms per cell and per day (p/c/d), resulting in protein titers above 5 g/l.


Nuclear Matrix CTCF Binding Chromatin Loop Imprint Control Region CTCF Binding Site 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Cori Gorman
    • 1
    • 2
  • Salina Arope
    • 3
  • Mélanie Grandjean
    • 3
  • Pierre-Alain Girod
    • 1
  • Nicolas Mermod
    • 3
    Email author
  1. 1.Selexis SAPlan-les-OuatesSwitzerland
  2. 2.DNA Gateway International, Inc.San FranciscoUSA
  3. 3.Laboratory of Molecular BiotechnologyUniversity of LausanneLausanneSwitzerland

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