Peter O’Callaghan, Ph.D.
Rachel Da Rosa, Ph.D.
In this interview, Lonza’s Peter O’Callaghan, Ph.D. (Senior Director, Head of Expression System Sciences) and Rachel Da Rosa Ph.D. (Associate Director, Product Management, Licensing and Early Access Services), address questions on the importance of DNA vector design in determining bioproduction outcomes, in addition to the benefits of using high performing, validated materials early in the development process to pave the way to IND and beyond. They also cover what expression solutions that we have developed to help ensure high titer, stable, and accelerated bioproduction.
Q: At a high level, why is the expression vector important in bioproduction?
PO’C: The first and very important step in recombinant protein expression synthesis, and assembly of a DNA expression vector that encodes the product gene(s). The expression vector acts as a critical set of genetic instructions that effectively tells host cells (in our case, Lonza’s CHOK1SV GS-KO® cell line) how to make a therapeutic protein, so the quality of this genetic instruction manual can play a key role in determining the overall success of a biomanufacturing process by influencing not only how much product the host cell produces, but also how well this product meets quality, regulatory and commercial needs.
Q: What are some of the early considerations that biologic drug developers must make to ensure a successful biomanufacturing process, and where can optimized vector design help address these?
RDR: Biologic drug developers face growing pressures from the early stages of development to accelerate programs as efficiently as possible while managing risk. Timelines, and importantly, efficiency, are particularly pressing in early development, where the generation of clinical material and progression to IND filing is a major milestone that may be linked to securing additional funding.
The use of optimized vectors at an early stage can reduce time spent on early material generation for tox studies, enabling higher and more stable expression levels alongside robust product quality that meets regulatory requirements. These early gains in efficiency not only accelerate the path to clinic, but also lay the foundations for commercially viable biomanufacturing. Therefore, selecting an expression system and vectors that can demonstrate these attributes early in development can increase the likelihood of long-term success for drug developers.
Q: How has Lonza evolved its expression vector platforms to address the needs of modern biologics development?
PO’C: At Lonza, we continuously innovate our expression systems to support the evolving needs of biologic drug developers. The GS Gene Expression System® platform offers a comprehensive toolbox of advanced vectors, scalable cell lines, and technologies designed to optimize and de-risk the development of biotherapeutic proteins.
We’ve made DNA vector design a major focus area in recent years. In 2019, Lonza acquired exclusive rights to use the hyperactive piggyBac® transposon technology in bioprocessing. Integration of GS piggyBac® technology into our vector platforms has consistently improved titers across a range of molecules, including more complex multi-chain formats.
Building on the successful integration of GS piggyBac® technology, Lonza further evolved its vector platform to support the efficient expression of complex multi-chain molecules. These GS piggyBac® multi-gene vectors enabled streamlined assembly of constructs containing up to four genes, while the subsequent introduction of the proprietary LHP-1 high-strength synthetic promoter further enhanced expression performance and productivity.
The latest addition, GS Ori-Go® vectors, represent a significant advancement in cell line development, combining simplified workflows with excellent productivity, stability and product quality both at a bulk pool and clonal level. By reducing time in the lab, enabling rapid scale-up and tox material supply, and supporting accelerated paths from gene to IND (in as little as six months*), they help drug developers move faster without compromising performance.
These advanced vector technologies, combined with our proven CHOK1SV GS-KO® cell lines and deep process expertise across the global Lonza network, help to optimize and accelerate the path from early development, through IND submission and scale-up, to commercial manufacturing.
Figure 1: Successive innovations in Lonza's vector platform have driven progressive gains in productivity, as demonstrated for this antibody.
To learn more about the science behind the new GS Ori-Go® vector system and how it can elevate performance and accelerate timelines, explore the scientific poster here.
Q: How can drug developers best leverage Lonza’s advanced technologies and expertise to maximize their chance of success?
RDR: It’s never too early in the development journey to adopt proven, scalable technologies that are familiar to regulators. From both scientific and commercial perspectives, initiating early-stage development with the GS Gene Expression System® can help to de-risk the path to IND and beyond. Leveraging a GMP-ready system from the outset can help to:
- Eliminate the need to switch to another cell line later in development, minimizing the risk of having to repeat development work, improving cost and resource efficiency and reducing the risk of delays
- Establish early confidence in critical attributes such as product quality, which may be more consistent when using the same platform throughout all development stages, and scalability
- Reduce regulatory risks by having a strong track record with GMP-compliant manufacturing
- Potentially increase investor confidence – biotherapeutic candidates developed using technologies with proven scalability, and a strong regulatory track record may be viewed more favourably by investors
- Ensure compatibility with CDMO platform processes for an easier transition to later-stage development when you’re ready to scale up
* Based on the use of pool material. From DNA transfection to delivery of IND-enabling CMC modules. Typical timelines. Subject to agreement with regulatory authorities.
The information contained herein is intended for general marketing purposes only. While Lonza makes efforts to include accurate and up-to-date information, it makes no representations or warranties, expressed or implied, as to the accuracy or completeness of the information provided herein and disclaims any liability for the use of this publication and that all access and use of the information contained herein are at their own risk. Lonza may change the content of this publication at any time without notice but does not assume any responsibility to update it. All trademarks belong to Lonza and are registered in Switzerland, EU and/or USA, or belong to their respective third party owners and are only being used for informational purposes.
