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> 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).
Cambridge, UK, 01 August 2017: Horizon Discovery (LSE: HZD) (“Horizon” or “the Company”), a global leader in the application of gene editing technologies, today 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.
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.
Dr. Darrin M Disley, CEO of Horizon Discovery Group plc, commented: “This programme, and the subsequent public release of our GS Knock-Out CHO K1 cell line, further reinforces Horizon’s leadership position in bioproduction and distinctive ability to drive innovation, both internally and industry-wide. Horizon’s open philosophy on sequence data, alongside our disruptive cell line licensing model, continues to challenge the industry and push the boundaries in bioproduction. It is our belief that greater innovation in the bioproduction space ultimately benefits the patient through enabling the commercial manufacture of therapeutics that would not be possible with existing solutions. Eagle Genomics has proven the ideal partner for this project, and we look forward to collaborating with them on similar ventures in the future.”
Abel Ureta-Vidal, CEO of Eagle Genomics, said: “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 difficult 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.”
Paul Flicek, Head of the Ensembl project at EMBL-EBI said “The Ensembl project at EMBL-EBI is pleased to offer a sequence of this quality and importance in the public domain. We are excited to partner with Horizon, Sanger and Eagle to offer this valuable new genome to the community and help speed innovation through further open scientific resources.”
Dr Thomas Keane, who led the sequencing team at the Wellcome Trust Sanger Institute*, said: “We are committed to scientific openness and data sharing and are very pleased to have produced the high resolution sequencing foundation for the public release of the CHO sequence data. This openness is an important aspect for us of our collaboration with Horizon, as the availability of the data will enable further research and development in the scientific community."
About Horizon’s Bioproduction platform:
Biological therapeutics made up seven of the top ten best selling drugs of 2015, and they feature extensively in developmental pipelines. Access to bioproduction cell lines for their manufacture can be cost prohibitive however, and is often restricted in ways that prevent their further optimisation by customers. This stifles innovation and means that drugs are not always getting to market due to the inability to generate bioproduction cell lines that meet the needs of commercial release.
Horizon is using its expertise in genome engineering to improve biological therapeutics manufacturing. As well as developing a tool box of cell lines for the manufacture of a range of current and next generation biological therapeutics, Horizon wants to encourage innovation in other organisations by allowing access to its state of the art bioproduction cell line platform (CHO SOURCE) under flexible licensing terms that include allowing the further modification of cells.
· Bioproduction: A type of manufacturing that utilises biological systems to produce commercially important biomaterials and biomolecules for use in medicines
· Biotherapeutic: A therapeutic material produced using biological means, for example an antibody
· CRISPR: A gene editing technology that enables genomic modifications in a wide variety of organisms and tissues with high efficiency
· Glutamine Synthetase: An enzyme that catalyses conversion of glutamate to glutamine, which is required for cell viability. This mechanism is used as a metabolic selection system linking expression of an exogenous GS gene to the expression of a protein of interest