Synpromics is collaborating with the Cell Therapy Catapult (CTC) to deliver a novel approach to producing stable cell lines for a variety of commercially relevant viral vectors.
​Creating next generation viral vector production systems to deliver higher titres and enable industrial-scale manufacturing of gene therapy products

Viral Vectors are Fundamentally Important in Cell and Gene Therapy

Viral vectors have become the main workhorse of gene therapy whether applied directly as medicinal products for in vivo genetic modification or in the ex vivo transduction of cells. Despite huge investment in cell and gene therapy and the fact that viral vectors are the current method of choice for gene modification, their manufacture is still extremely problematic. Manufacturing processes rely on adherent cell lines and transient transfection; unfortunately transfection of suspension cultures is very inefficient and costly requiring large quantities of plasmid DNA. These methods are not suited for scale-up and rely on the scale-out of the unit operations for supply of larger clinical trials. Current batch sizes limit both the size of trials and the indications that can be investigated. Switching to suspension based expansion of the packaging cell line would significantly improve the ability to scale-up the manufacturing processes.

Synpromics' Technology Can Enhance the Production of Viral Vectors

Synpromics is creating cell lines with synthetic promotors that drive higher productivities, but also allow inducible expression of toxic viral proteins providing a significant advantage over the current transient constitutive systems. The inducible systems developed allow a two phase bioprocess: rapid cell expansion without the burden of virus production and then an intense virus production phase.

Synpromics is applying its technology with CTC with a view to developing novel scaleable manufacturing processes and technologies for the production of high titre viral vectors. The collaboration is focussing on the development of a toolbox of constitutive and inducible promoters custom-designed for maximum activity.

The major limitation of efficient viral vector production is that the most common vectors are still mainly produced using transient transfection systems, which is a consequence of the cytotoxicity induced by some of the components required for their production. Therefore, Synpromics is using its technology to create suitable inducible promoters to enable the production of stable producer cell lines for three classes of viral vector: Retrovirus, Lentivirus & AAV. The intention is to increase the productivity of producer cells (and decrease the costs of virus) by overcoming the need for multiple transfections for each manufacturing run. Ultimately, viral vector production will be able to be turned on and off as needed and so the promoters will be tightly controlled with small molecules giving robust process control.