Synthetic LethalomeTM

Rethinking cancer mutations

At Gordion, we consider all tumor mutations found in Exome and in the Dark Genome. 98% of mutations are found in the Dark Genome, but these are typically ignored in drug program design.

Synthetic Lethality

A gene mutation, typically results in multiple other genes becoming essential for tumor survival a phenomena called Synthetic Lethality. Tumors accumulate ~15,000 mutations, yet this complexity is not covered by existing methods for finding synthetic lethal targets and assess drug resistance.

Synthetic Lethality between gene A and B occurs when loss of both genes leads to cell death

Synthetic Lethality is strongly dependent on other mutations accumulated by a tumor

Synthetic lethalome™

The Dark Genome is where majority of these 15,000 mutations are found. Using these data gives us an unique opportunity to build the Synthetic Lethalome™ - a comprehensive Atlas of Drug Targets for all tumor mutation sets.

Our Platform utilizes advanced Machine Learning to assess tumor-specific selection pressure on potential targets
and constructs Dark Genome descriptor models to validate the relevance of target candidates.

Application of Synthetic lethalome™

This approach allow us to find promising new targets that are synthetically lethal with mutated genes including established high-interest p53, MYC, KRAS where drug discovery has had limited success. By applying Machine Learning directly to Exome and Dark Genome data, the Platform can identify which genes and pathways become essential as a result of the primary gene mutation. From these now-essential, Synthetic Lethal genes, the best druggable targets can be selected.

Inhibition of Gordion001 is cytotoxic to KRAS cancer cells in vivo

Synthetic lethalome™

An Atlas of tumor specific essential genes for all mutation sets.

If you’re interested in assessing the placement of your CRISPR screen results within the Synthetic Lethalome, please: