Tell us about your academic and professional background and how it led to co-founding SynGenSys. Where did the idea for the company first come from?
For the past two decades, I’ve been based at the University of Sheffield as Professor of Bioprocess Engineering, leading a research group focused on the production of high-value next generation biomedicines - recombinant protein biopharmaceuticals produced by CHO cells and AAVs for gene therapy made by HEK cells.
We have collaborated with a variety of bioindustrial partners, and have utilised UK Government Reseach Council funding to develop novel technologies for improved biomanufacturing. Operating at the biology-engineering interface, my team has undertaken a wide range of projects; from genetic engineering of mammalian cell factory function using synthetic biology and functional genomics, to the development of new bioprocessing technologies.
About 10-15years ago, we used mathematical modelling based on analysis of industrial CHO cell lines to determine which cellular synthetic processes limited recombinant monoclonal antibody production by CHO cells. We showed that the cellular process of transcription – the conversion of DNA into mRNA in the nucleus of cells (and which underpins modern biotechnology)– ultimately governs how much product cells could produce. We knew then that we had to develop a new technology to control and accelerate this in order to improve cellular productivity.
My colleague Adam Brown and I began developing synthetic promoters, new pieces of DNA designed to replace traditional, unpredictable viral elements such as the cytomegalovirus (CMV) promoter commonly used to drive transcription in mammalian cells. Our synthetic promoters offer stronger, tuneable control of recombinant gene transcription.
It became clear that our synthetic promoter technologies had real commercial value and broad application potential. In 2021 we formed SynGenSys, meaning Synthetic Genetic Systems, a company dedicated to delivering better outcomes for advanced therapies and biomanufacturing.
What makes Sheffield attractive as a hub for life science and biotech research, and how is being based at the University enabling SynGenSys’ development?
Firstly, Sheffield is a really great to place to live! The University of Sheffield is an ideal environment that fosters innovation in biological engineering and life-sciences. A Russell Group University ranked among the world’s top 100, Sheffield is also part of the White Rose Consortium, a regional research powerhouse connecting Sheffield with Leeds and York, offering a huge network of expertise in molecular biology, bioinformatics, and biotechnology. Sheffield also offers exceptional depth of research expertise and facilities across engineering, bioscience and medical disciplines, further supporting SynGenSys’ R&D, and allowing us to recruit a talented, multi-disciplinary, local team.
To translate research, the University has a well developed Commercialisation Journey, a structured programme to help innovators spin out their technology. The programme was instrumental in attracting external investment and provided vital early stage support for SynGenSys; we were able to access pre-seed funding from both the University and the Connecting Capabilities Fund - Northern Triangle Initiative. We later secured investment from angel investors and multinational companies, enabling us to accelerate the development of our platform and commercialise our technology.
How does SynGenSys' approach differ when serving the biomanufacturing industry versus the cell and gene therapy space?
For biopharmaceutical manufacturing, we offer a new paradigm for the critical process of cell line development (CLD). CLD aims to create genetically engineered mammalian cell factories capable of making protein products in sufficient quantities. However, CLD is not always sufficient for more complex protein products. Using our platform, we are able to engineer promoters, tailoring them to the desired product in order to improve cell factory productivity.
In cell and gene therapy (CGT) the promoter becomes an integral part of the therapeutic DNA payload itself, either introduced into the body (in vivo) or cultured cells (in vitro). Crucially, the promoter determines whether a delivered therapeutic gene is active in a specific cell type or tissue or not. Our technology allows CGT developers to use synthetic genetic parts that are only active in target cells, at an optimum level, providing an inherently safer solution for patients and enabling development of next-generation, precisely targeted advanced therapies.
In both applications, we harness our powerful computational platform, which enables in silico bottom-up design and engineering of novel, fit-for-purpose genetic sequences, like promoters. Importantly, users can define specific requirements up front (such as tissue on/off targeting) and we mine huge amounts of genetic information to design new synthetic genetic assemblies with predictable functionalities.
What are scientists doing at the moment that you think your technology can improve upon? Do you think there are any barriers to adoption?
We are working to make our technologies as simple to deploy as possible for developers of new biomedicines and advanced therapies, without extending development times or increasing costs. In fact, we can potentially save biopharmaceutical developers significant sums of money in development time and manufactring costs. For CGT, tissue-specific control of therapeutic gene expression(mediated by synthetic promoters for example) to improve safety and efficacy would perhaps be a logical regulatory requirement.
Ultimately, our technology minimises risk, and associated with this, cost. The risk that new biopharmaceuticals cannot be made or will require extended development times, and the risk that gene therapies are not as safe and efficacious as they could be. It all begins with our computational design systems. There are no real barriers to adoption other than a general lack of awareness of our technology. This is something we are very actively working on!
What have been the team’s most significant milestones since the founding of SynGenSys? What can we expect from SynGenSys in the future?
We have achieved several major milestones since founding the company, including a successful seed funding and the expansion of our commercial team. We’ve filed multiple biomanufacturing patent applications and extended our R&D efforts to include signal peptides, as well as commercially launching cell-specific promoter libraries such as CHO.SET and NK.SET.
Our next phase focuses on commercial expansion, strengthening industrial collaborations, scaling our platforms, and stronger engagement with both the biomanufacturing and CGT sectors.
Ultimately, our mission is to empower companies to bring next generation medicines to patients faster, safer, and more efficiently than ever before.
