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Knowledge Exchange on NGS-Based Cell Line Development

May 28, 2021
Marie-Ange Kouassi

Genedata aims to bring together experts in the field of NGS-Based Cell Line Development to share experiences at open forum events. The recent open forum on April 29th, 2021, co-hosted with Boehringer Ingelheim (BI), featured representatives from over 20 leading international biopharmaceutical companies. Following an introduction on the strengths and possibilities of NGS in CLD by Jan Visser, Vice president of Bioprocess Development Biologicals at BI, speakers presented case studies highlighting their current activities in CLD and shared their perspectives on the future possibilities of this technique. Innovative biopharmaceutical companies have already begun leveraging NGS for variant analysis of cell lines, gene knockout characterization as well as multi-omic data integration and analysis. However, there is still a clear need to exchange knowledge and best practices to facilitate faster adoption of this technique in the industry. At the open forum, there was a highly engaged audience and fruitful discussion demonstrating the high demand for learning new methods of improving cell line development in the biopharmaceutical industry.

Benjamin Lindner, Senior Data Scientist at Boehringer Ingelheim discussed the importance of genetically characterizing CHO cell lines as a crucial requirement for therapeutic biologic production. His presentation highlighted the advantages of using RNA-Sequencing as an alternative to Sanger sequencing. Advantages of RNA-Seq include a superior sensitivity for mutation detection. Also, it is a highly specific, repeatable, and robust technique. Implementing RNA Sequencing results in a streamlined laboratory workflow, delivers a scalable approach, and reduces the uncertainty of personal evaluation by providing an unsupervised automated bioinformatic analytical approach. Finally, future perspectives were shared which include the use of single-cell RNA sequencing (scRNA-Seq) to assess cellular heterogeneity of clonal cell lines.

Rico Uhler, Data Scientist in Cell Line Development at Octapharma Biopharmaceuticals demonstrated the benefits of NGS-based methods for the characterization of gene knockouts. A case study was presented where the goal was to improve the pharmacokinetic properties of human embryonic kidney cells (HEK cells) which displayed problematic expression. This expression was highly disadvantageous as it significantly reduced the half-life of protein-based pharmaceuticals in development. Through Targeted Locus Amplification (TLA) and validation using Genedata Selector®, complex genomic arrangements were identified that were not detectable using amplicon sequencing. Methods of generating fully functional and optimal clones with knockouts at specific, desired sites were also described.

Another important topic of discussion at the CLD open forum was multi-omic data integration and analysis led by Kitty Agarwal, Principal Scientist in Biologics Process Development at Bristol-Myers Squibb. Leveraging this approach has proved beneficial in enabling faster and predictive bioprocess development at biopharmaceutical companies particularly while embracing complex modalities such as multi-specific antibodies. The need for new technology and omics analyses to improve mechanistic understanding of how cell lines can be modified to achieve the best product was also discussed. Some challenges of multi-omic data integration highlighted include data storage and management as well as the ability to draw actionable scientific insights efficiently. A data science service project in collaboration with Genedata was described which involved long and short-read sequencing in the Genedata Selector platform offering a high-quality genome assembly. Additional outcomes involved hot spot identification for targeted transcriptomic and epigenomic integration. Finally, Kitty Agarwal elaborated on the advantages of leveraging artificial intelligence and machine learning to draw conclusions from high-dimensional data.

Overall, the open forum provided a platform for discussion regarding the applications of NGS in cell line development. With a range of questions asked related to scientific, manufacturing, and regulatory topics, scientists had the opportunity to discuss experiences using novel technologies sharing challenges and best practices. To fill the knowledge gap and help to achieve industry standards in implementing NGS in cell line development and biosafety, Genedata Selector will continue hosting regular open forums alternating between the two areas. Be sure not to miss the next open forum event on NGS-based Cell Line Development or Biosafety.

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