Synpromics is focused on improving the industry’s viral vector manufacturing in two ways. The first is through a collaboration with the Cell and Gene Therapy Catapult (CGTC) to deliver a novel approach to producing stable cell lines for AAV and lentivirus biomanufacturing. The second is through the in-house development of constitutive and inducible promoters for use in viral vector manufacturing that are currently available for out-licensing.

Viral Vectors are Fundamentally Important in Cell and Gene Therapy

Dynamic Range of Constitutive Promoters

Synpromic’s design platform has enabled the creation of a suite of constitutive promoters for use in bioprocessing and viral vector manufacturing. This suite of promoters has a 50-fold dynamic range, from many times stronger than commonly used viral promoters to very weak. This large range of promoters allows for the fine-tuning of expression level to obtain the optimal yield from the manufacturing process.

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 promoters 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 CGTC with a view to developing novel scalable 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.

Inducible Promoters for BioProcessing

Synpromic’s design platform allows the creation of strong, highly responsive and tightly regulated promoters controlled by either addition of a safe small molecule or via changes in the cellular environment. These promoters allow the development of new processes for traditionally problematic proteins/viruses and provide the tools to overcome the bottlenecks in current bioprocessing and viral vector manufacturing.

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.

Synpromics' novel approach to synthetic promoter development means that it is now possible to develop new promoters to tackle the biotechnology challenges of viral vector manufacturing. We can either select and out-license candidates from existing promoter libraries or alternatively engage in a design and development program to deliver promoters with particular criteria that are unique to the specific application.