by Neil Taylor, Ph.D.
Principal Scientist, Early Development Services
In the fast-paced realm of pharmaceuticals, the pursuit of groundbreaking therapies relies on pioneering drugs and cutting-edge technology. Our Early Development Services (EDS) team are at the forefront of just this - combining science and progress.
World-leading technology
As a Principal Scientist responsible for genetic analysis of customer cell lines, I’m passionate about molecular biology and excited to be part of a team that uses innovative genetic analysis technologies.
Our team innovates new technology to ensure the data we generate stays relevant - not just today, but in the ever-evolving landscape of pharmaceutical regulation. My approach, inspired by this ethos, helps the team to adopt the most progressive and pertinent methodologies available in genetic analysis.
Advanced genetic analysis for regulatory submissions
Genetic analysis is a long-established prerequisite for regulatory submissions, as emphasized in the 1996 ICH (International Council for Harmonisation) Q5B guidelines.
The guidelines require that:
“the nucleotide sequence encoding the product should be verified” and “suitable techniques should be used to analyze the expression construct for copy number, for insertions or deletions, and for the number of integration sites.”
Fortunately, the authors had the foresight to understand that analysis methods: “should be periodically reviewed to take advantage of new advances in technology..”
Recognizing the need for continuous evolution has allowed our team to stay aligned with the guidelines’ recommendations and embrace novel technologies.
Leading the implementation of digital PCR techniques
At EDS, I led the implementation of Digital PCR (dPCR) and Droplet Digital PCR (ddPCR) techniques for precise gene copy number determination. This sensitive method detects nuanced changes during cell line stability studies and tracks rare variants in cell populations - enhancing accuracy and providing profound insights into genetic alterations within cell lines.
Transitioning from traditional sequencing to RNASeq
Transitioning from traditional sequencing methods to the more comprehensive RNASeq marked a pivotal moment in the team's genetic analysis endeavors. Traditional techniques often fell short in detecting aberrant transcripts. However, RNASeq emerged as a sensitive next-generation sequencing method capable of uncovering unexpected gene fusions and providing comprehensive insights into product gene expression levels.
Adaptability is key
My role in the EDS team goes beyond adoption, encompassing troubleshooting, adaptation, and the creation of novel strategies to help tackle unforeseen challenges in cell lines and customer projects. Adaptability is key to the role and aligns with my commitment to innovation and willingness to explore uncharted territories within advanced genetic analysis. Having this flexible approach allows our team to identify new approaches and strategies to questions that we were never expecting.
The future of advanced genetic analysis
Looking to the future, I expect the integration of long-read sequencing technologies. This will help address some of the current limitations in mapping repetitive sequences, offering a comprehensive understanding of vector integration within genomes, and helping to shape the future of genetic analysis.
Next-generation sequencing techniques
The transformative potential of RNASeq assays for early-stage screening will play an instrumental role in unraveling the complexities within cell lines. Implementing NGS (Next Generation Sequencing) techniques in the early developmental stages offers a peek into the enigmatic black box of cell lines, potentially enabling the rational design and accelerated development of high-performing cell lines.
Delivery of superior medicines, faster
As we navigate the ever-evolving landscape of genetic analysis in cell line development, my hope is that our dedication will continue to help steer the industry towards a future where breakthroughs are not just occasional - but the norm.
About the author:
Neil is a Principal Scientist in Early Development Services, Cambridge, UK with a special interest in the Molecular Biology aspects of projects. Neil studied Biochemistry at Birmingham University, UK and completed his PhD there, before Post-Doctoral positions at Aberdeen, UK, Leuven, BE and Cambridge, UK, focusing on proteolysis within the secretory pathway. He has been with Lonza for eight years and has extensive experience in expressing and troubleshooting complex protein projects. Neil also developed Lonza's current Genetic Characterisation service.