Rational CHO cell engineering

For stable recombinant protein expression and production
Biotechnology
Genetics & Cancer

Many of the bestselling medicines are recombinant proteins produced by CHO cells with many more mammalian-cell-derived recombinant therapeutic proteins in development.

Progressive improvements in manufacturing technologies — from genetic vector engineering to process engineering — have substantially intensified production processes, enabled control of product molecular heterogeneity and importantly, reduced development time. A key issue for CHO cell utilisation is genome plasticity, rearrangement and instability that often result in the loss of the transgenes. We have discovered a number of robustly stable, highly-expressing genomic sites into which we have engineered a landing pad platform.

Application

  • Potential to improve industrial recombinant protein production.

Development Status

We have demonstrated efficient site-specific recombinase-mediated insertion of genetic constructs into the landing pad site on a CHO chromosome to enable the stable expression of proteins for an extended period of time:

  • Stable protein expression observed > 1 CHO cell line
  • Proof of concept demonstrated with a marketed monoclonal antibody therapeutic: stable protein expression seen for >120 generations.
  • Easily adaptable recombinase system to test production of any target protein.

IP Status

  • Patent application filed 10 December 2020.

Commercial Offering

  • We welcome approaches from interested parties to discuss collaborative research and licensing opportunities.

Opportunity

Existing technology relies on the biologic expressing transgenes integrating randomly into the host chromosome which results in highly variable protein expression between transfectants. The advantages offered by the genomic locations identified enable the stable expression of proteins over many generations which is critical for replicable industrial protein production processes.

Technology

Edinburgh researchers have engineered CHO cell lines to stably produce high quantities of protein through the identification of novel hot spots to enable exogenous nucleic acid sequences to be targeted to these sites for stable protein expression.

Benefits

  • Potential to increase protein expression levels resulting from the identification of more suitable locations for stable protein expression.
  • Stable protein expression has been observed over multiple generations.
  • Genetically stable sites which are free of silencing.
  • Confidence in replicable protein titres over a high number of generations and between batches.
  • Increased cell line growth rate observed in one cell line.

Publication


Header image: Microscope image of cells with stable GFP expression at one of our newly defined genomic locations.

Quote: TEC1104272

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Paul Clarke

Technology Transfer Manager
School of Biological Sciences
The Roslin Institute
College of Veterinary Medicine