If there’s one lesson I’ve learned throughout my scientific career, it’s that some of the most meaningful innovations begin by questioning assumptions that have been accepted for years.
The GS Gene Expression System® platform has been the foundation of cell line development at Lonza for more than three decades. It has enabled the commercialisation of 100+ recombinant therapeutic proteins and has continually evolved to meet the changing needs of our customers.
Yet, like many mature and highly successful technologies, certain elements of the system had remained consistent over time, providing an opportunity for targeted innovation. One of those elements was the way glutamine synthetase expression was controlled. While methionine sulfoximine (MSX)-free stable cell selection has gained traction across the industry for CHO cell line development, achieving this within the Lonza’s GS® platform while maintaining stringent glutamine synthetase selection stringency required a new level of innovation to deliver enhanced performance without MSX.
For many of us working with the technology, the question wasn’t simply how to improve performance – it was whether we could fundamentally rethink a part of the system that was already working well.
That question ultimately became the beginning of the journey that led to GS Ori-Go® vectors.
Looking beyond incremental improvements
Innovation rarely happens through a single breakthrough. More often, it involves a surprising number of whiteboards, discarded hypotheses, and coffee.
That journey eventually led me, together with Peter O’Callaghan, to develop the core concept behind what is now the GS Ori-Go® vector system. This vector design is based on the novel combination of the bacterial origin of replication (Ori) sequence, which has been repurposed as a control element for glutamine synthetase transcription, synergistically working in combination with the downstream synthetic promoter LHP-1.
Over several years, the team explored different approaches to improving GS® vector design. Earlier advances, including the development of new promoters, demonstrated that there was room to further enhance the performance of the GS System® platform. At the same time, new concepts around vector architecture were beginning to emerge. Individually, these innovations showed promise, but it was only when they were brought together that we realised we might be able to achieve something far more significant.
The resulting design fundamentally changes the way cell line development can be approached. By enabling a direct transition from transfected bulk cell pools to clonal cell line development, the GS Ori-Go® vector system removes the need for intermediate high-producer screening and MSX selection. Simplifying the workflow not only saves valuable development time but also improves consistency and reproducibility throughout the process.
Looking back, the solution seems remarkably elegant, and frequently elicits customer feedback such as “how on earth did Lonza come up with that?!”. Getting there, however, required countless experiments, learning valuable insights from unexpected results, and steadily refining the system.
From concept to customer impact
The most satisfying moment in any innovation project isn’t when the final experiment succeeds – it’s when the technology begins making a difference.
Since April 2026, the GS Ori-Go® vectors, as part of the GS Gene Expression System® platform, have been implemented across all cell line development projects within Lonza’s Integrated Biologics business. The results have been encouraging. The platform has demonstrated lead clone titres exceeding 11 g/L, improved productivity across multiple modalities by more than 30%, maintained stable pool expression over 30 generations and enabled a DNA-to-IND timeline in as little as 6 months.
These improvements are more than performance metrics. For our customers, they represent earlier decision-making, reduced development risk and greater confidence during one of the most challenging stages of biologics development. As part of Lonza’s enhanced DNA-to-IND offering, the GS Ori-Go® vector system helps accelerate the journey from discovery to clinical development while maintaining the quality and robustness that customers expect from the GS Gene Expression System® platform.
Beyond the breakthrough
Developing the GS Ori-Go® vector system has reinforced something I believe is true across scientific research: even technologies with decades of success can still surprise us.
Progress doesn’t always come from starting over. Sometimes it comes from looking at familiar problems with fresh eyes, asking different questions and having the courage to pursue ideas that initially seem ambitious.
I’m also still impressed by what so many talented colleagues accomplished together. Peter and I may have originated the concept, but transforming it into a robust platform required the skills and dedication of an exceptional team – Malak Ammar, Sophie Wensley, Avinash Srivastava, Changhavi Ragurajan, and many others.
While I’m proud of what we’ve accomplished, what excites me most is what comes next. If the GS Ori-Go® vector system helps our customers bring promising biologic therapies to the clinic faster and with greater confidence, then the years spent challenging long-held assumptions will have been well worth the effort.
