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Compositions and Methods for Increasing Recombinant Protein Yields through the Modification of Cellular Properties

Posted Aug 31 2008 5:00pm

Description of Invention:
This technology relates to compositions and methods for improving the growth characteristics of cells engineered to produce biologically active products such as antibodies or glycosylated proteins. Featured is a method that uses gene candidates (e.g., cdkl3, siat7e, or lama4), or their expressed or inhibited products in cell lines, such as Human Embryonic Kidney (including HEK-293), HeLa, or Chinese Hamster Ovary (CHO). The gene expression modulates growth characteristics, such as adhesion properties, of the cell lines thereby increasing recombinant protein yields and reducing product production costs.

This technology may be used to improve production of therapeutic and/or diagnostic compounds, including therapeutic proteins or monoclonal antibodies from mammalian cells. Optimization of mammalian cells for use as expression systems in the production of biologically active products is very difficult. For certain applications, anchorage-independent cell lines may be preferred, whereas for other applications, a cell line that adheres to a surface, e.g. is anchorage-dependent, may be preferable. This technology provides a method for identifying a gene whose expression modulates such cellular adhesion characteristics. This method thus leads to an increase in the expression or yield of polypeptides, including therapeutic biologicals, such as antibodies, cytokines, growth factors, enzymes, immunomodulators, thrombolytics, glycosylated proteins, secreted proteins, and DNA sequences encoding such polypeptides and a reduction in the associated costs of such biological products.

This technology offers the ability to improve yields and reduce the cost associated with the production of recombinant protein products through the selection of cell lines having:
  • altered growth characteristics
  • altered adhesion characteristics
  • altered rate of proliferation
  • improvement in cell density growth
  • improvement in recombinant protein expression level

Development Status:
Late Stage - Ready for Production

Joseph Shiloach (NIDDK)
Pratik Jaluria (NIDDK)

Patent Status:
HHS, Reference No. E-149-2006/2
PCT, Application No. PCT/US2007/018699 filed 24 Aug 2007
US, Application No. 12/438,706 filed 24 Feb 2009

Relevant Publication:
  1. P Jaluria et al. Application of microarrays to identify and characterize genes involved in attachment dependence in HeLa cells. Metab Eng. 2007 May;9(3):241-251. [ PubMed abs ]

Licensing Status:
Available for licensing.

Collaborative Research Opportunity:
The National Institute of Diabetes and Digestive and Kidney Diseases, Biotechnology Core Laboratory, is seeking parties interested in collaborative research projects directed toward the use of this technology with cells for drug and vaccine production and development, including growth optimization, production and product recovery processes. For more information, please contact Dr. Joseph Shiloach, , or Rochelle S. Blaustein at .

Infectious Diseases
Infectious Diseases - Diagnostics
Infectious Diseases - Therapeutics
Infectious Diseases - Vaccines
Infectious Diseases - Research Materials
Infectious Diseases - Other

For Additional Information Please Contact:
Peter Soukas J.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325 Room 14,
Rockville, MD 20852-3804
United States
Phone: 301-435-4646
Fax: 301-402-0220

Ref No: 1552

Updated: 09/2008

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