Case Study : Horizon Discovery
Eagle Genomics collaborated with Horizon Discovery on the release of high quality, well annotated CHO genome
Over the past 30 years, the pharmaceutical industry has substantively redesigned every part of the bioproduction process, considerably improving productivity. However, in this time the CHO cell itself, arguably the greatest potential source of efficiency improvements, has remained largely unchanged.
The CHO genome was first sequenced in 2011; however, the current annotation is not suitable for whole-genome screening. Together with licensing terms that restrict modification of the cells, this has meant that progress in cell-line improvement has been slow. This has been a source of considerable frustration among drug manufacturers, as there has been increasing interest in improving productivity through cell-line innovation since the emergence of gene-editing tools such as CRISPR.
To address this problem, Horizon and its partners – the Sanger Institute and Eagle Genomics – have established a high-quality sequence map based on Horizon’s GS Knock-Out CHO K1 cell line which was chosen as the basis for this project as it is manufacturing-ready, and licenses come with the right to modify the cells, which is highly unusual among commercially available GS CHO KO cells. Eagle Genomics was commissioned to complete the high quality genome assembly and gold standard gene annotation of the data for the project, using their cutting-edge technology in close collaboration with the Ensembl group at the European Bioinformatics Institute (EMBL-EBI).
By releasing this sequence into the public domain, Horizon hopes to enable genuine quality-by-design in bioproduction cell-line development, through the widespread ability to identify genes that, if modi ed, could improve the phenotype of interest.
This sequence empowers Horizon’s continuous innovation process, supporting the identification of targets that may lead to future iterations of the cell line. Additionally, Horizon has developed a range of services to directly support customers’ internal efficiency improvement efforts.
Horizon Discovery is a global leader in the application of gene editing technologies. The sequencing project was undertaken as part of the Biocatalyst Funding awarded jointly to Horizon, University of Manchester and the Centre for Process Innovation (CPI). The Biocatalyst Funded project is focused primarily on large-scale gene editing to improve CHO host performance, which in turn required specific high-resolution sequencing of the Horizon GS knockout CHO host.
“Eagle Genomics has proven the ideal partner for this project, and we look forward to collaborating with them on similar ventures in the future.”
Dr. Darrin M Disley, CEO of Horizon Discovery Group plc
“Genome assembly and annotation are essential to genomic data innovation and to drive product development. Unfortunately, generating a CHO reference genome of sufficient quality for applications like genome engineering has been notoriously di cult due to aneuploidy and complex chromosome rearrangements of the cell line. Our analysis of high-quality source data using multiple bioinformatics methods in a robust QC framework was able however to produce a reference that materially improved on previous efforts. It is gratifying that now, for the first time, a commercially available bioproduction cell line can be directly paired with its detailed reference genome and we believe this will be vital to unlocking the potential of the cell lines.”
Abel Ureta-Vidal, CEO of Eagle Genomics