Advanced analytics for biopharma using nanopore sequencing | LC26

Abstract
Biologics encompass a diverse range of customizable agents (mRNAs, cell lines, and viral products) derived from living organisms. Both their evolution as well as their ever-expanding number of applications mark a transformative shift in modern medicine. Nevertheless, inherent risks, including potential contamination and the precision and stability of the applied genetic modification, challenge their production and therefore, adequate quality control (QC) should be applied. With easier assembly, better annotation capabilities, and improved potential to map inserts and epigenetic modifications, long-read sequencing emerges specifically as an unmatched QC tool for biologics compared to current state-of-the-art methods. Therefore, OHMX.bio is currently developing and optimizing library preparation workflows and bioinformatic software pipelines for the QC of the following agents starting from Oxford Nanopore Technologies (ONT) sequencing: 1. mRNA vaccines, based on cDNA sequencing to check integrity, purity, and identity (including capping and polyA tailing) of the products. 2. Recombinant cell line characterization, to meticulously pinpoint integration and modification events. 3. In the near future, a pipeline is planned for the QC of adeno-associated viral (AAV) products with a focus on genome integrity, inverted terminal repeat (ITR) typing and impurity profiling. Current setup is demonstrated in a research context, but with the intention to move in time to the good manufacturing practice (GMP)-tailored environment and sequencer present at OHMX.bio. Together, these emphasize the effectiveness of long-read sequencing for robust and validated QC, essential for the upcoming evolutions in industrial therapeutic biologics.

Biography
Steven Verbruggen graduated as a bioscience engineer specialized in bioinformatics for high-throughput technologies. In his PhD, he focused on the development of bioinformatic tools for multiomic research. He is currently leading the BioIT side of OHMX.bio. In this role, he applies his expertise to ensure the team comes up with the most optimal custom solutions for customers’ biological questions. He strives to keep the company up to date with the latest data analysis strategies for its cutting-edge omics technologies.Abstract
The advent of mRNA in therapeutics has allowed more rapid engineering of targeted therapies, the safety and efficacy of which are dependent upon mRNA identity, integrity, and purity. The measurement of these mRNA critical quality attributes (CQAs) currently requires a panel of analytical methods, some of which require molecule-specific development. Lonza is collaborating with Oxford Nanopore Technologies (ONT) to bring streamlined, multi-attribute methods into the current good manufacturing practice (cGMP) environment. As platform methods that can measure multiple CQAs in a single assay with fast turn-around times and no upstream development, they will accelerate the optimization of mRNA manufacturing and the path to market of mRNA products.

Biography
Amanda Hughes obtained her PhD in Biomedical Sciences from the University of Massachusetts Medical School, after which she performed postdoctoral work at the University of Dundee and EMBL Heidelberg. In 2024, Amanda joined Lonza as a project manager and lead scientist, focused on validating ONT sequencing equipment and methods for use as multi-attribute, platform methods in QC.