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Drug Discovery and Development

Genomic and proteomic science has advanced tremendously over the past decade, which has led to the development of 'targeted' therapeutics and companion diagnostics that leverage knowledge of an individual’s genetic makeup to create a more personalized approach to healthcare. 

It enables drug developers and providers to identify who is susceptible to which health conditions; determine how a given patient will respond to a particular therapy; and match newly developed drugs to patients based on their genetic profiles. This approach promises to eliminate unnecessary treatments, minimize the potential for adverse events, and ultimately, improve the outcomes for patients, drug developers and payers alike.

The translation of genomic discovery into practical drug discovery, diagnostic, prognostic and theranostic tools requires the development of accurate laboratory-based models that recapitulate the various genetic events identified as significant in human disease onset and progression. Such models can be employed in target identification, target validation, cell-based screening, lead optimization, drug re-positioning, and patient responder profiling regimens to support the rational development of targeted or personalized medicines.

Horizon’s GENESIS™ confers the ability to rapidly introduce subtle, yet highly significant ‘gain-of-function’ disease mutations (common in many forms of disease), as well as loss-of-function alterations, into any endogenous gene loci of human cells; thus accurately and definitively modelling a real patient’s diseased versus normal state.

X-MAN™ cell lines contain key genetic variations that define a patient genotype engineered into human cells. Furthermore X-MAN™ pathway reporter cell lines can be engineered that enable functional cell-based assays to be carried out at the endogenous level, looking at natural levels of protein and promoter activity, a critical element of biologically-relevant studies.

Horizon has deployed X-MAN™ cell lines and X-MAN™ reporter cell lines in a wide range of assays that include specialized disease microenvironment assays enabling analysis of parameters such as hypoxia, 3-dimensional growth, senescence, autophagy and drug resistant pathway responses.

These assays clearly demonstrate the role that endogenous mutations play in driving disease and reinforce the importance of placing these cells under disease-relevant conditions in order to illicit the true disease phenotypes and drug responses seen in the clinic.  

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