Proteines - Import export

Delphi Genetics offers the benefits of its proprietary Staby® technology through partnering opportunities. We intend to build high-value strategic collaborations for exploring the benefits of the Staby® technology in various DNA & Protein bioproduction settings. Partnering is a key component of our service delivery strategy. Delphi Genetics is open to consider any collaborative projects at all stages of development from R&D to the commercialization of your bioproduct. We seek collaborative partnerships with Biotech & Pharma companies that could enable us to contribute to your development on either a risk-sharing or out-licensing basis. In order to consolidate a long term relationship with its partners, Delphi Genetics is currently developing a brand new GMP production facility. This mid-scale capacity facility will join technology and flexibility to provide plasmid DNA and protein with high value for your clinical phases.

For manufacturing recombinant proteins or DNA, plasmid instability is a significant concern. Typical biomanufacturing processes in prokaryotes require the use of bacterial plasmids as vectors carrying the gene of interest to be over-expressed. It has been demonstrated that the growth of plasmid bearing cells is significantly reduced relative to plasmid free hosts, simply because protein production represents a significant burden on cellular metabolism. This is of significant concern in the Biopharmaceutical Industry as both the yield and the production reproducibility of recombinant molecules are significantly lowered by that fact. Antibiotic resistance genes are the most common selectable markers used in fermentation processes to avoid plasmid free cells to overgrow the culture. However antibiotics are expensive compounds and they (or their degradation products) can contaminate the biomass or production product.

In order to maximize protein expression, the Staby® system was combined to the proven T7 polymerase technology for the over-expression of recombinant proteins: the gene of interest is under the control of the T7 promoter. This combination is called StabyExpress®. The pStaby1 plasmid contains the gene encoding the antidote protein (ccdA) which counteracts the action of the ccdB protein. The SE1 strain, in which the ccdB selection gene is inserted in the chromosome in order to stabilize the pStaby1 plasmid has been engineered by Delphi Genetics as a dedicated bacterial strain for protein expression and is derived from BL21(DE3). Consequently, IPTG has to be used to induce protein expression, an alternative strategy being the use of an auto-inducible medium (such as Delphi Genetics' Staby®Switch medium). Staby®Express ensures that only plasmid-bearing clones can grow whereas every clone losing the plasmid will inevitably die.

Several alternative strategies have been developed to minimize the risk that plasmid-free cells overtake the culture. One of the most promising of those strategies relies on the use of postsegretional killing genes (so called poison / antidote genes or selection modules) that induce host killing upon plasmid loss. Delphi Genetics has designed a novel and highly effective stabilization system, called Staby®, based on the use of selection modules naturally found in plasmids, bacterial chromosomes and bacteriophages. A selection module (like the ccd system used by Delphi Genetics) is typically organized as an operon and composed of two genes: the ccdB selection gene codes for a small stable protein which is toxic for E. coli, whereas the ccdA antidote gene codes for a small unstable protein that neutralizes the toxic protein both transcriptionaly and via protein-protein interactions. This unique system allows for the perfect stabilization of the plasmid without the use of antibiotics