AACR 2025 Poster: AI-Driven Discovery of Novel Synthetic Lethal Gene Pairs for Targeted Cancer Therapy

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Conclusions

• In summary, using EditCo's high throughput automated cell line engineering platform, EditCo generated 72 knockout pools in less than 3 weeks to validate novel SL gene pair relationships
• In silico modelling of cancer dependency data identified the next generation of druggable synthetic lethal gene pairs
• We have prioritised gene pairs with a rational mechanism linking the target and biomarker, and with patient populations with high levels of unmet need
• These pairs reflect both pan-cancer and highly lineage specific relationships
• We have validated >10 of these relationships across multiple cell lines to give high confidence in the validity of the novel pairs
• For one gene pair with FAK as the druggable node we have generated novel inhibitors with best-in-class selectivity over the SL partner and properties suitable for in vivo dosing and validated the specific targeting of biomarker low cell lines