Animal Cell Technology - Research Activities

Mammalian Cell Technology

Viral Vector Technology

Biosystem Analysis, Process Analytical Technologies and Process Control

Mammalian Cell Technology

Contact: Yves Durocher
Tel.: (514) 496-6192
E-mail: yves.durocher@cnrc-nrc.gc.ca

Mammalian cells are the host of choice to produce recombinant proteins for therapeutic use. The Mammalian Cell Technology group as a strong expertise in developing processes using stable clones (CHO, HEK293, hybridoma, etc) for the production of r-proteins. In addition to using stable clones, the group has developed a robust large-scale transfection technology that allows production of milligram to gram amounts of r-proteins from cDNA in less than ten days in a human cell line. This technology is routinely operated in serum-free medium at the 45 L scale and uses a proprietary HEK293 cell line. The group has succeeded in producing and purifying a vast array of secreted, intracellular and membrane-associated proteins using this technology. Major increase in the expression yields of r-proteins have been obtained following key improvements in the expression vector, cell line, culture medium and process. The use of the green fluorescent protein (GFP) and secreted alkaline phosphatase (SEAP) as reporters demonstrated that more than 60% of suspension-growing cells could be transfected and that over 70 mg/L of SEAP could be produced five days after transfection. The group has also successfully used the large-scale transfection technology for the production of adenovirus-associated virus (AAV) at the 3 L scale.

Viral Vector Technology

Contact: Amine A. Kamen
Tel.: (514) 496-2264
E-mail: amine.kamen@cnrc-nrc.gc.ca

Viruses are powerful means for delivering genes, and as a result there is growing interest around the world in their potential use in gene therapies. The Animal Cell Technology group is developing robust, scalable and cGMP-compliant integrated processes for the production and purification of recombinant viral vectors for gene delivery. The viral vectors of interest are adenovirus (AV), adeno-associated virus (AAV), retrovirus (RV) and baculovirus (BacMam), all of which offer potential as viral vectors for gene delivery. The group is developing processes with SF9 insect cells (derived from the fall armyworm) for BacMam and AAV, and HEK293 cells for AdV, AAV and RV. The research team has succeeded in developing a 100 L suspension serum-free medium process for large-scale expression of recombinant adenovirus vectors. In addition, it has developed a new process with a HEK293-based packaging cell line for retroviruses. The group has also developed scaleable chromatography techniques for the purification of viral vectors

Biosystem Analysis, Process Analytical Technologies and Process Control

Contact: Robert Voyer
Tel.: (514) 496-6337
E-mail: robert.voyer@cnrc-nrc.gc.ca

The Animal Cell Technology group aims to develop strategies to implement large-scale production processes, using online monitoring tools and off line data from biochemical analysis. The group used existing online monitoring tools and advanced process control algorithms to achieve high cell density processes. New tools are being developed, such as acoustic filter based perfusion processes with transformed mammalian and insect cells as well as real-time monitoring of physiological states of the cells and feed-back control of animal cell cultures. In addition, the group uses metabolic flux analysis in order to identify limitations for growth, targets for metabolic engineering studies and implement changes in feeding strategies and media composition.

Related Information

Institutes:

• NRC Biotechnology Research Institute