Horizon Discovery

Horizon's target identification platform SyntheTx™ sees convergence of three powerful technologies:

GENESIS™, which enables the generation of human isogenic disease models that accurately recapitulate the genetics of specific target patient populations
X-MAN™ in vitro phenotypic assays that provide a cancer related environmental context to the diseased versus normal genetic state
High-throughput siRNA and shRNA library screens to uncover novel targets with inherent anti-cancer activity and rational patient stratification approaches

Synthetic Lethality: Loss of either gene A or gene B in normal cells is compensated by action of the remaining gene. Lethality occurs in tumor cells when a mutation in one of these genes leaves the cell vulnerable to loss of the other gene by inhibtion:

Enlarge Image

Deploying X-MAN™ cell lines in cell-based synthetic lethality screens enables the identification of putative patient populations that exhibit downstream genes/proteins that represent novel targets of therapeutic intervention.

These technology platforms enable the performance of simple, high-throughput and rational RNAi screens to be performed that:

Give definitive information on identifying patients who manifest the drug target and will benefit from therapeutic intervention
Provide inherent information (by virtue of the presence of a matched normal genetic background in the screen) that those gene target hits identified will have tumor selective properties and will have a clear therapeutic window and mode of action

X-MAN™ models are currently available that cover the majority of the 300 most common cancer mutations but there is much work to do to map the entire cancer genome landscape with less common genotypes.

These models are essential to understand how cancer genes affect pathways and to define the next generation of drug targets that demonstrate selective anti-cancer effects.