Horizon Discovery

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Horizon Discovery Group plc

Type	Public limited company
Industry	Biotechnology
Founded	2005 (2005)
Founder	Prof. Alberto Bardelli, Dr. Chris Torrance
Headquarters	Cambridge , United Kingdom
Number of locations	4
Area served	Worldwide
Key people	Terry Pizzie (CEO), Ian Gilham (Chairman of Board of Directors, 2014)[1]
Products	Isogenic cell lines Engineered Haploid cell lines (HAP1) Reporter Kits Molecular Reference Standards Model organisms
Services	Custom cell line development using rAAV, ZFN and CRISPR Specialized assay services Drug screening services Target identification and validation Combination High-throughput screening (cHTS) Bioproduction
Number of employees	400
Website	Horizon Discovery

Horizon Discovery Group plc (LSE: HZD) ("Horizon"),^[2] is a gene editing company that designs and engineers genetically modified cells and then applies them in research and clinical applications that advance human health.

Horizon builds human disease models and reagents derived from genetically-engineered cells that its customers use, or that are deployed on their behalf to: gain knowledge of the genetic drivers of disease; develop novel drugs or cell therapies targeted at these genetic drivers; and develop companion diagnostics that predict patient response in the clinic. In this way they apply genetic knowledge to provide biological insights that translate to improved research and development outcomes for drug developers and treatment regimens that better serve patients.

Horizon has an international customer base of over 1,400 unique organisations across more than 50 countries, including major pharmaceutical, biotechnology and diagnostic companies as well as leading academic research centers. The Group supplies its products and services into a range of markets, estimated to be worth over £29 billion in 2015.^{[citation needed]}

Horizon is headquartered in Cambridge, UK, and is listed on the London Stock Exchange’s AIM market under the ticker “HZD”.

Horizon signed agreements in December 2019 and January 2020 with Mammoth Biosciences to combine Mammoth's intellectual property in CRISPR with Horizon's expertise in Chinese hamster ovary cells.^[3]

Perkin-Elmer acquired Horizon Discovery for $383 million (£296 million) in November 2020.^[4]

Gene Editing[]

Gene editing is the process by which specific changes are made to the sequence of a gene within the context of a host cell. By editing the code of a patient-derived cell to introduce or repair a genetic change believed to drive disease, a patient’s disease can be reproduced in a laboratory setting, letting researchers ask important biological questions of potential drugs or cell therapies earlier in the drug discovery process.

Tremendous research efforts have gone into identifying and refining the tools used to generate engineered human cell lines. These fall into two categories based on their biological approach:

• Gene editing mediated through homologous recombination (e.g. rAAV), which takes advantage of a cell’s natural DNA repair mechanism through ‘DNA crossover events ‘to perform precise genome alterations through highly targeted insertions
• Gene editing mediated through double strand DNA break repair (e.g. CRISPR, ZFN), which generate a cut in DNA, after which a cell’s natural DNA repair mechanisms fix the break, during which errors can occur or modified sequence can be introduced

Each technology has its own features and strengths and it is these differences that make each best suited for addressing different gene-editing challenges.

Horizon has taken a ‘technology agnostic’ approach, developing deep experience and taking multiple licenses for rAAV, CRISPR and ZFNs, letting the company choose the right approach for any project.

• Recombinant Adeno-Associated Virus (rAAV) can be used in a genome editing platform that uses rAAV vectors to enable insertion, deletion or replacement of DNA sequences in a cell's genes. Horizon has an exclusive global license for research applications for this technology.
• Zinc Finger Nucleases (ZFNs) are engineered DNA binding proteins that can be designed to bind to a wide variety of DNA sequences and function by introducing a double stranded break at a specified location in the genome. Horizon has licensed this technology from Sigma-Aldrich for use in custom in vitro and exclusively for in vivo gene-editing projects.
• CRISPR/Cas9 is an RNA-guided gene-editing platform derived from Streptococcus pyogenes that makes use of an endonuclease (Cas9) and a synthetic guide RNA to introduce a double strand break at a specific location within the genome. Horizon has licensed IP from Harvard University, the Broad Institute and ERS Genomics with the goal of being able to ensure uninterrupted use of this technology to customers.

Through its gene editing platform, Horizon is able to alter genes in virtually any human or mammalian cell line. Based on this, Horizon now offers over 23,000 cell line pairs that accurately model the mutations found in genetically based diseases.

These ‘patients-in-a-test-tube’ are being used directly by customers, or by Horizon on their behalf, to identify the effect of individual or compound genetic mutations on drug activity, patient responsiveness, and resistance, which may lead to the successful prediction of which patient sub-groups will respond to currently available and future drug treatments.

Once built, engineered cells can also act as product manufacturing engines, yielding related cell and reagent products that can be used by customers as research tools or molecular diagnostic reference standards or as a means to generate advanced in vivo models, or even as factories for the manufacturing of protein-based therapeutics.

In this way, the cells power Horizon’s entire business of Products, Services and high value Research Biotech initiatives.

Businesses[]

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Horizon operates through three business units; Products, Services and Research Biotech. Products and Services are offered under the following brands:

• Cell Lines: Horizon offers a catalog of more than 23,000 gene edited cell line pairs that can be used to study the role of any gene in a variety of cellular processes and thus provides a tractable model for the study of human gene function.
• HDx Reference Standards: Horizon is a leading provider of genetically defined, human genomic reference standards, including Formalin-Fixed Paraffin-Embedded (FFPE) cell line sections and purified genomic DNA (gDNA), as a sustainable source of reference material to laboratories, proficiency schemes and manufacturers.
• SAGE in vivo Models: Horizon Discovery acquired Sage Labs in 2014 and now partners with the leading minds in neurobiology, cardiobiology, immunology and toxicology to develop next-generation preclinical models for advanced disease research.
• CHO SOURCE Biomanufacturing Cell Lines: Horizon provides products and services that aim to revolutionize the production of large molecule therapeutics, providing innovative and accessible solutions for all organizations of all sizes.
• Pathfinder Research Services: Pathfinder Research Services include precision gene-editing, isogenic cell line assays, cutting edge screening platforms and in vivo models to help solve your research and drug development challenges.

References[]