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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.
About Horizon Discovery Group plc www.horizondiscovery.com
Horizon Discovery Group plc (LSE: HZD) ("Horizon"), is a leading global gene editing company that designs and engineers genetically-modified cells and then applies them in research and clinical applications that advance human health.
Horizon’s core capabilities are built around its proprietary translational genomics platform, a highly precise and flexible suite of gene editing tools (rAAV, ZFN, CRISPR and Transposon) able to alter almost any gene sequence in human or mammalian cell-lines.
Horizon offers over 23,000 catalogue products and related research services, almost all of which are based on the generation and application of cell and animal models that accurately recapitulate the disease-causing genetic anomalies found in diseases like cancer. Horizon’s commercial offering has been adopted by over 1,600 unique research organisations in over 50 countries as well as in the Company’s own R&D pipeline to support a greater understanding of the genetic drivers of disease and the development of molecular, cell and gene therapies that can be prescribed on a personalised basis.
Horizon is headquartered in Cambridge, UK, and is listed on the London Stock Exchange’s AIM market under the ticker “HZD”.
About Eagle Genomics www.eaglegenomics.com
Eagle Genomics is a smart data management software company helping life sciences companies conducting data intensive research to bring new candidate medicines, therapies and products to patients and customers more quickly. Its Automated Data Scientist platform puts state of the industry data science at the fingertips of biologists to radically reduce time to cost of research, thus enabling customers to achieve drastic productivity improvements and true data driven discovery.
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...
Collaborations in biotechnology
Commercial and academic collaborations are used throughout the biotechnology and pharmaceutical sector to enhance research and product development. Collaborations can take the form of research and evaluation agreements, licensing, partnerships etc. ...