KRAS is one of the most frequently mutated genes in cancer, but targeting KRAS with potent small molecules has proved to be difficult. Moreover, although inhibitors of BRAF and MEK, which are downstream targets of KRAS, have been developed, they have transient benefits only in patients with melanoma who have mutated BRAF. Therefore, an effective therapy for KRAS-driven tumours remains a pressing unmet medical need.
The discovery of the CRISPR‐Cas system in bacteria has initiated an impressive array of innovations that have enabled the use of the RNA‐guided Cas9 nuclease in functional genomic screens. At Horizon, we have embraced these developments, as they provide new opportunities for drug target identification and validation. The case studies presented in this below highlight how we use this technology to successfully conduct genome wide and focused sgRNA library screens and to verify whether specific genes are required for the survival and/or proliferation of cancer cell lines.