SynpromicsThe explosion in the field of synthetic biology is causing ripples across the biotech industry. In today’s guest blog, David Venables and Michael Roberts of Synpromics, discuss the impact of synbio on another exciting area of biotech, gene therapy, by reducing the cost and increasing the scale and efficiency of viral vector manufacturing.

Synthetic biology is a relatively new discipline within the biotech industry, having leapt onto the scene only a decade ago, largely to address specific needs arising in the industrial biotechnology sector. There have been many definitions put forward over the years, but synthetic biology is broadly accepted as being the application of engineering principles to biological processes to improve and exploit them for commercial gain. A number of small start-ups are leading the field, and there is a strong entrepreneurial spirit akin to that seen in the IT sector. The vision is that all biological parts can be standardised and taken ‘off-the shelf’ to build complex biological systems that can be used to improve upon various industrial or, more recently, biomedical processes.

The synthetic biology landscape in Europe

The synthetic biology landscape in Europe, SynBioBeta

Synpromics is a synthetic biology company. We have IP and knowhow in the design of synthetic promoters – stretches of DNA just upstream of a gene that determine protein transcription/translation efficiency. Our synthetic promoters are designed to enable the controlled expression of genes under specific conditions: in a specific place or environment, or in response to a specific biological condition.

At the beginning of this year, we were delighted to announce a collaboration with the Cell and Gene Therapy Catapult, to remove a major barrier to the development of the cell and gene therapy industry by reducing the cost, and increasing the scale and efficiency of viral vector manufacturing. The collaboration will use our synthetic promoter design technology, and the Cell and Gene Therapy Catapult’s flexible manufacturing platform to create stable producer cell lines for the high titre and large scale manufacture of viral vectors. The work will be part funded by a £2m grant from Innovate UK.

Applications of synthetic biology

Applications of synthetic biology, SynBioBeta

Viral vectors are a crucial tool needed to modify patient’s cells to create a therapeutic effect. Established manufacturing platforms are limited by laborious processes, a lack of automation and low yields. This restricts the utility of viral vectors for the treatment of diseases where large amounts of virus would be needed, and has to date confined their use to local applications such as in the eye and to less prevalent indications, including orphan diseases.

This project will use synthetic biology to develop novel and controllable gene-expression promoters to drive the production of a much higher level of viral vector yield from new stable cell lines. This will allow the industry to produce vectors to much higher titres and with more efficiency, removing the current constraints associated with plasmid transfection of anchorage dependent cell lines.

For instance, these constraints particularly limit the manufacture of AAV-based viral vectors, where vector batches are currently produced from very low culture volumes (often only a few hundred litres). AAV is now the vector of choice in a number of clinical protocols as it mediates long-term gene expression, efficiently infects a number of different cell types and elicits a reduced immune response compared to previously used vectors. If AAV is to be widely adopted in the clinic then it is imperative that larger batches can be made in bioreactors to much greater scale (i.e. approaching tens of thousands of litres).

The project will run for three years, and will be focused on developing prototype cell lines to deliver industry relevant viral vectors, including Retrovirus, and Adeno Associated Virus. Synpromics will be responsible for the expression platform development with the Cell and Gene Therapy Catapult responsible for process industrialisation and control.

This will be the fifth major collaboration for Synpromics to apply our synthetic promoters in gene therapy. We believe Synpromics’ technology will provide a critically needed solution to high titre, industrial scale, vector manufacture, a critical barrier in the gene therapy industry. The result of this solution will be a major advance to the commercialisation of gene therapies in non-orphan drug indications.