Microbial Cell Line Development

An effective, high-quality and fully characterized expression cell line as well as comprehensive documentation are crucial for the success of a scientific idea from the first laboratory experiments to the production, registration and/or commercialization of a biological product.

ARTES develops the most efficient solution for the client’s recombinant protein target of choice.

Microbial cell line development, troubleshooting and project managing

We minimize project risks and optimize outcomes with the help of high-quality toolboxes, innovative and state of the art methods and techniques.

Our vaccine technology platforms based on enveloped virus-like particles (eVLPs) or capsid virus-like particles (cVLPs) combined with our efficient and proven microbial expression platforms are the best choice to economically produce a safe and effective vaccine that meets your needs.

We compile a complete documentation of the materials that you can use for your registration process.

Our offer is embedded in a transparent, well-defined project design. It includes the definition of deliverables, timelines, milestones, Go/No-go decision points and costs.

The project as such typically starts with the design of genes optimized for the respective microbial host. After a first answer on the feasibility of expression, the next steps may include the generation of stable cell lines, optimization of expression and/or secretion, selection of production cell line(s) for transfer resp. for further process development at ARTES. Genomic characterization and preliminary high cell density fermentation are the next steps in the project design.

Yeast cell line development

Cell line development for your recombinant protein of choice is possible in several yeast strains. We offer strain generation in our proprietary host Hansenula polymorpha (syn. Pichia angusta), in  Pichia pastoris, Saccharomyces cerevisiae or other yeasts.

Hansenula polymorpha is one of the most important industrial expression systems. This high quality yeast is known for commercial production of products approved by US-FDA, EMA, EFSA and several non-regulated market authorities. The WHO has recommended Hansenula-based vaccines for mass vaccination programs.

Hansenula differs from other yeasts in its ability to form stable cell lines and to integrate very high copy numbers of the respective expression cassettes. Hansenula fermentation processes are characterized by the absence of expensive inducers (MeOH-free), animal components and/or antibiotics. This makes these processes the basis for cost-effective commercial production.

We own all relevant intellectual property rights, backed by years of unpatented know-how. We ensure 100% freedom to operate for all customers and licensees and guarantee a smooth and high standard project progress.

For the identification of your cell line with the highest productivity and the required quality for your product, we use:

 Hansenula expression platform:

  • large toolbox (hosts, expression vectors, secretion signals, chaperones)
  • high-copy integration exceeding other yeast systems (up to 120 copies per cell)
  • co-expression of multiple genes
  • 100% stability of all production cell lines for so far > 25 years
  • absence of allergens, endotoxins and viral contaminations
  • secreted products without contaminating host cell proteins (> 90% purity in fermentation broth)
  • high yield production of intra-cellular soluble proteins
  • metabolic engineering for design of whole-cell biocatalysts
  • antibiotic resistance free host vector system
  • scale-up production/fermenation

E. coli cell line development

Escherichia coli is the most popular host for protein expression due to its ease of cultivation, rapid growth rate, and well-established genetic tools.

One of its main advantages as a host for protein expression is its ability to produce large quantities of protein quickly and cost-effectively. Additionally, genetic modifications can easily be made in order to optimize protein expression and increase yield. E. coli also has a simple nutrient requirement, making it an ideal candidate for large-scale industrial protein production.

For the expression of your recombinant protein in a bacterial system, we provide a highly efficient E. coli platform. Depending on the specificities of your target molecule, we design a package including the screening of different parameters such as promoters, expression strains and the conditions of the expression. Our platform is characterized with a host/vector toolbox allowing selection of the optimal production cell line and most cost-efficient expression mode.

We are experienced with purification, solubilization and refolding of proteins from inclusion bodies, which often occur if a strongly expressed recombinant protein forms insoluble protein aggregates in the cytoplasm of E. coli. Inclusion bodies can be exploited as a valuable source of functional proteins which are usually highly pure and can be obtained in large quantities.

 E. coli expression platform

  • large toolbox (different hosts, constitutive and inducible promoters, signal sequences for periplasmic expression)
  • inexpensive set-up and costs
  • short timelines
  • high productivity
  • fast, parallel expression screening
  • 1-step purification
  • Endotoxin assay and removal
  • purification and refolding of proteins from inclusion bodies
  • scale up production/fermentation