The project aims to investigate genomic risk loci for coronary artery disease (CAD) and stroke in both in vitro and in vivo settings, and to determine whether any are suitable targets for therapeutics.
Horizon will work with Leicester University to engineer the candidate genomic risk loci into normal human cell lines (induced pluripotent cells and differentiated endothelial and vascular smooth muscle cell types) in order to study which SNP-variations have a predisposing impact towards cardiovascular disease. Horizon will use its GENESIS™ genome editing platform to engineer the cell lines, which now includes an expanding array of guided-nuclease techniques (ZFNs and CRISPR) alongside its proprietary precision rAAV-mediated homologous recombination technology. This project will expand Horizon’s panel of isogenic X-MAN™ human disease model cell lines into a new therapeutic area, in which genetics are thought to play a significant role alongside other environmental factors such as diet and exercise.
The consortium will then carry out molecular profiling of the genome-edited cell lines. This will include analysis of locus-specific and global gene expression (using microarrays) to define biological pathways impacted by each risk variant, complemented by analysis of relevant proteins. These data will be integrated with those from other investigators involved in the project, examining pathways in relation to genotype at a tissue level.
“By developing a better understanding of which inherited genetic variations represent true risk loci it is hoped that a more focussed and rigorous approach to disease prevention can be taken. The investigation of genomic risk loci may also inform the design of future targeted therapies that aim to get at the root of genetic predispositions for these conditions,” commented Chris Torrance, Founder and CSO, Horizon Discovery.
Other groups involved in the project and each receiving a share of the grant include: Deutsches Herzzentrum München, University of Leicester, Oxford University, UMC Utrecht, LMU Munich, University of Lübeck, Bioceros, Clinical Gene Networks, European Screening Port, 4SC Discovery, and Genedata.
Leicester University is a member of Horizon’s network of Centers of Excellence (CoE) for genome editing.
About Horizon Discovery www.horizondiscovery.com/
Horizon Discovery Limited (Horizon) is a leading provider of research tools to support translational genomics research and the development of personalized medicines. Using GENESIS™, Horizon is able to alter any endogenous gene sequence of a human or mammalian cell-line quickly, reliably and without introducing unwanted and confounding genotypes and/or phenotypes.
Horizon has applied GENESIS to create over 500 X-MAN™ cell lines, the world’s first source of genetically-defined and patient-relevant human cell lines, accurately modeling the disease-causing mutations found in cancer patients. These ‘patients-in-a-test-tube’ are being used by academic and industry leaders to identify the effect of individual or compound genetic mutations on drug activity, patient responsiveness, and resistance, leading to the successful prediction of which patient sub-groups will respond to currently-available and future drug treatments. This enables the design of shorter, more focused, and less expensive clinical trials, ultimately providing the tools to identify the ‘right drugs’ for the ‘right patients’ based upon the unique genetic mutations that define their disease.
In addition to X-MAN cell lines, Horizon provides GENESIS and X-MAN derived products and services, with industrial application in: bio-pharmaceutical process optimization; clinical diagnostic development; drug discovery & development; and the provision of reference standards for genomic-based clinical research platforms.
GENESIS and X-MAN are registered trademarks of Horizon Discovery Limited.
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Email: c.claxton@horizondiscovery.com
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