Horizon Releases High Quality, Well Annotated CHO Genome Sequence sequence to Drive Innovation in Bioproduction

Horizon Discovery (“Horizon” or “the Company”), a leader in the application of gene editing technologies, announced it has released a complete, high-quality, well annotated sequence of its GS Knockout CHO-K1 bioproduction cell line. The sequence will be made available publicly via the Ensembl website at EMBL-EBI, to serve the community as a resource to drive research and innovation in bioproduction at Horizon and across the industry.

•         Genome sequence is based on Horizon’s Glutamine Synthetase (GS) Knock-Out CHO K1 manufacturing-ready cell line.

•         Sequenced in collaboration with the Wellcome Trust Sanger Institute, this high value reference tool enables the industry to screen for genes associated with desired phenotypes and to help drive innovation in bioproduction.

•         Horizon commissioned Eagle Genomics 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).

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. 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 modified, could improve the phenotype of interest.  

Horizon’s GS Knock-Out CHO K1 cell line 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. The use of Horizon’s cells alongside the public sequence thereby provides the ideal base and dataset to enable screening that can provide immediately actionable results. The public sequence can also be applied to any other CHO cell line; however, additional validation of sequence may be required to confirm the cell line being used does not differ in any meaningful way from the public sequence.

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. To achieve this, Horizon collaborated with the Sanger Institute to achieve the detailed genome sequencing needed, and selected Eagle Genomics to deliver the complex annotation of the genome assembly.

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.