What inspired the founding of SynGenSys, and how did your academic background lead you to this point, particularly into the field of transcriptional control?

Academic research, is, and should always be, high risk. We should be solving very complex problems with a high risk of failure. I trained as a bioengineer, and my early academic research focused on the development of useful technologies that can improve the manufacture and performance of biopharmaceuticals, specifically by engineering promoters.  

We eventually got to the point where we were routinely running projects with major biopharma partners, and the platform technologies we developed were producing  better results than other commercially available options. It then made sense for us to transition to a commercial entity, enabling other scientists to take advantage of the technologies we have created. Forming a company allows us to ensure wider adoption of our technology, to maximise real-world impact.

Transcription is central to almost every human disease and biological medicine that has ever gone into a patient. Whether producing monoclonal antibodies or delivering gene therapies, transcription is key to both how treatments are developed and how they function in patients. As an engineer, the focus is always on solving the core problem. When the challenge lies in transcription, the solution is to engineer the elements that control the process, like promoters, to effectively address the problem.

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Can you share some of your published research that has ultimately led to the work SynGenSys is doing today?

Our first published piece of work with industry was a paper with UCB in 2014 on synthetic promoters for CHO cell engineering, which ultimately laid the the groundwork for our CHO.SET promoter library. We then collaborated with AstraZeneca on a large project looking at improving protein production in CHO cells. A key output was the development of synthetic promoters, which AstraZeneca patented and utilized in-house. In academia, it’s common to receive positive feedback on research, but it’s rarer to see immediate, practical use in industry. Confirmation that our technology worked in real-world applications to solve bioproduction challenges inspired us to form SynGenSys.

While we have explored various technologies in our research groups, promoter design stood out for its clear industrial demand. Our work demonstrated that we could create DNA sequences that reliably solve problems, offering tangible value and paving the way for the company.

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What are the key challenges SynGenSys is addressing in biopharmaceutical development and production?

While specific challenges vary for different classes of molecules in biopharmaceutical development, ultimately it all boils down to one question: can you produce enough of the product at requisite quality and safely deliver it to the patient? In manufacturing, this often means optimising yield, product quality, and predictability. Here, promoters play a critical role in balancing the expression of different protein chains, ensuring efficient production and economic viability.

In gene therapies, the focus also includes safety and ensuring genes are expressed at the right levels, in the right cells, and not in unintended locations.

Essentially, SynGenSys addresses all the key bottlenecks: improving yield, ensuring consistent quality, and providing precise control of gene expression.

 

Can you give us a brief overview of the SynGenSys platform and what makes it unique compared to in-house expression systems or other promoter technologies?

A key differentiator of SynGenSys as a company is that almost every member of our team is a biopharmaceutical engineer. We've developed technologies for all parts of biopharmaceutical production and design, cell engineering, media engineering, and other biological components. Our promoter design platform, Sypher, considers every aspect of how DNA components behave over their lifecycle, from initial design to long-term use in industry. Every base pair is engineered for predictability, safety, and performance, minimising the risk of failure downstream.

Our platform is also highly data-driven. By applying the engineering cycle of design-build-test-learn across many projects, we’ve built extensive datasets that inform accurate, multi-objective DNA design. Even small sequences of base pairs can have billions of possible combinations, and each base can impact performance. Sypher optimises entire sequences rapidly and reliably, offering significant advantages and enabling confidence in our designer promoters, as well as offering the potential to expand this out to other genetic components.

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What significant milestones has your team achieved so far, and what’s next in the Development of your platform?

A major achievement for us is the speed of our promoter design process. What once took years in an academic context now takes only six to nine months, with the design process itself now taking around two months and delivering a much more tightly defined set of promoters for lab testing than was ever possible before.. We also have several exciting projects in the pipeline – keep an eye on our news page for updates!

We’ve recently expanded our platform to include signal peptides, complementing our promoter technology. Signal peptides play a key role in directing proteins to their intended cellular locations and can significantly impact protein production, for example by improving secretion outside the cell or enhancing protein folding efficiency. This has a range of potential application areas including biologics manufacturing (i.e. enhanced folding can increase yield and quality), and cell and gene therapies (e.g. optimised processing of target proteins can enhance therapeutic efficacy).This allows us to optimise protein production more effectively, whether using promoters, signal peptides, or both.

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How has being based at University of Sheffield facilitated SynGenSys’ growth as a biotech startup?

The University of Sheffield ranks among the world’s top 100 universities, providing access to world-class facilities and expertise that would be cost-prohibitive for a startup to replicate independently. As a research-intensive university, it provides us access to equipment like flowcytometry and mass spectrometry, as well as a steady stream of talented researchers, from undergraduates to postdocs, who often transition into the company. The university also has a proud history in engineering and remains particularly renowned in that field as a leading civic university. It is very supportive of spinouts, which has been invaluable for our growth.

 

Do you plan to continue with your academic career alongside your role at SynGenSys? What are your longer-term ambitions?

Yes - being in academia allows me to continue tackling high-risk, innovative problems that go beyond the company’s current focus. Long-term, I will continue supporting SynGenSys’ growth as we develop novel solutions for gene expression control, while also  developing technology for other fields across biopharmaceutical engineering.

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