Columbia Technology Ventures

High-throughput approach for base editing the kinome

This technology is a high throughput genome editing approach for selective and endogenous inhibition of all kinases utilizing base editing.

Unmet Need: Selective genetic modeling approach for endogenous kinase inhibition

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.

The Technology: High-throughput base editing method for endogenous kinase 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.

Applications:

  • Targeted cancer therapeutics
  • Genetic screens modeling kinase inhibition
  • Research tool for studying kinase function and regulation
  • Base editing screens for novel druggable target
  • Drug screening for small molecules

Advantages:

  • High-throughput base editing
  • Comprehensive gRNA library for kinase inhibition
  • Applicable to other enzyme classes
  • Versatile
  • Fast screening and easy handling

Lead Inventor:

Neil Vasan, M.D., Ph.D.

Patent Information:

Patent Pending

Related Publications:

Tech Ventures Reference:

  • IR CU24051, CU22283, CU24053, CU24052

  • Licensing Contact: Jerry Kokoshka