Horizon Discovery

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.

• 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.

Horizon operates through three business units; Products, Services and Research Biotech.