This technology is a high throughput genome editing approach for selective and endogenous inhibition of all kinases utilizing base editing.
Current genome editing technologies often involve knockdown or knockout of the entire gene which does not mimic enzymatic inhibition by small molecule drugs and cannot provide detailed mechanistic insights into gene function. For example, some kinases have no phenotype when knocked out, but when catalytically inhibited (using genetic knock-in) cause lethality. These genetic knock-in strategies to inhibit kinase activity are not scalable to date. Further, these approaches are mainly used for therapeutic purposes such as editing mutant DNA in diseased patients but are not useful for studying the effects of specific mutations on cell growth and gene expression. There are currently no genome editing approaches that support high-throughput, selective, and endogenous enzyme inhibition.
This approach specifically inhibits kinases through base editing of amino acids that are necessary for catalytic activity. A library of guide RNAs targeting catalytic sites for all kinases in the kinome is curated and ready to use. This technology enables high throughput modeling of endogenous enzyme inhibition that mimics small molecule inhibition and can be used in pooled screens to interrogate how specific kinase activity regulates cell growth, sensitivity to targeted therapies and potentially identify novel kinase for therapeutic targeting.
This technology has been validated with human cancer cell lines.
Patent Pending
IR CU24051, CU22283, CU24053, CU24052
Licensing Contact: Jerry Kokoshka