Location: Cambridge, UK

28/08/2018

• Co-development and implementation of a new CRISPR-based screening technology platform to address critical gaps in target ID and validation
• Single cell RNAseq-linked pooled CRISPR screening offers unparalleled depth of screening data and biological insight
• New platform will further enhance Horizon’s CRISPR screening capabilities

Cambridge, UK, 28 August 2018: Horizon Discovery Group plc (LSE: HZD) ("Horizon", "the Company", or "the Group"), a global leader in gene editing and gene modulation technologies, today announces that is has entered into a collaboration with a global pharma partner to co-develop and apply a novel cutting-edge research tool for target identification and validation.As part of this collaboration, Horizon will lead the development and application of single cell RNAseq-linked pooled CRISPR screening using a key discovery paradigm of the pharma partner. Horizon will use the development process, acquired infrastructure, and optimization data in order to further develop and improve these tools to offer to future partners, as part of its research services operations.Functional genomic screening with CRISPR-Cas9 technology has provided a powerful and precise way to identify and validate novel drug targets, and to elucidate unknown drug mechanisms. The depth of biological insight possible from Horizon’s single cell RNAseq-linked CRISPR screening platform will allow researchers to ask far more complex experimental questions and speed up the time from discovery to validation by integrating the effect of gene editing with complex phenotypic signature mapping. With this technology, pathways, biomarkers and cell function can all be studied and revealed with ultra-rich data.Horizon’s pooled format screens offer researchers access to highly robust whole-genome level analyses that yield outstanding data quality. Whilst this approach has proven a potent research tool, it is currently challenging to adequately multiplex the analysis from these screens to evaluate complex biological phenomena. Coupling pooled screening to single cell RNAseq however, allows the opportunity to address the impact of CRISPR-based gene modification on a global transcriptomic level, at single cell resolution. This enables customers to address critical gaps in target identification and validation as they work to develop novel and more effective drug therapies.“Pooled CRISPR-Cas9 knockout screens have rapidly become an important tool in novel drug target identification and validation. Horizon continues to innovate in this important area, having launched our CRISPR interference (CRISPRi) and CRISPR activation (CRISPRa) screening service in 2017, and through the development of RNAseq-linked CRISPR screening,” commented Terry Pizzie, Chief Executive Officer, Horizon Discovery. “The co-development of this tool with a major pharma partner provides a substantive advance to Horizon’s already world-leading screening capabilities, offering our customers cutting-edge solutions not available elsewhere.”More information about Horizon’s CRISPR screening platforms and the quality of data these produce can be found at: https://www.horizondiscovery.com/research-services/functional-genomic-screening/crispr-screening.- ENDS -About Horizon’s High-throughput Functional Genomic Screening platform:Horizon has established a core expertise in functional genomic screening using CRISPR-Cas9 and RNAi screening platforms. These techniques are used to explore the function of genes by interrupting their sequence or disrupting the process by which they lead to the generation of protein. In this way, these screens can be used to find and validate novel drug targets, to identify mechanisms of drug resistance or sensitivity, and to aid with patient stratification. Horizon performs these screens in both normal human cell lines and also in haploid cell lines, which represent a simplified and efficient model with which to explore gene function as these cells have only one copy of each gene. Horizon’s CRISPR platform includes CRISPR knockout, which uses gene editing to effect function, as well as CRISPRi and CRISPRa. CRISPRi, which induces gene repression, and CRISPRa, which activates gene expression, provide powerful applications for CRISPR screening. CRISPRi screening is especially well suited to study the function of genes that when knocked out are essential for cell survival, or that are amplified to provide a functional effect, both classes of genes that are not amenable to CRISPR knockout screens. CRISPRa screening enables, for the first time, the study of activation-linked responses on genome-wide level.Glossary:

• RNAsequencing (RNAseq): the using of next generation sequencing to quantitatively study the expression level of specific genes via the level of mRNA in the cell
• CRISPR: A gene editing technology that enables genomic modifications in a wide variety of organisms and tissues with high efficiency
• CRISPRa and CRISPRi: Nuclease deficient versions of Cas9 that enable the repression or overexpression respectively of target genes
• Functional Genomic screening platform: A platform used by Horizon to identify and validate genes as targets for novel therapeutics using CRISPR based screening and other approaches
• Knockout: Genetic technique in which one of an organism’s genes is made inoperative.

Source: https://www.horizondiscovery.com/about-us/news/collaboration-with-major-pharmaceutical-company-on-single-cell-rnaseq-linked-crispr-screening