Science Pool

CRISPR-Cas9 in Drug Discovery

The journey from a bacteria defence mechanism to a leading tool in modern biomedical research is often a long one. One exception to this has been the development of CRISPR-Cas9 technology. Originally discovered in its components as early as 1987, it reached the realms of a technology tool at the beginning of the last decade and was awarded the Nobel Prize in 2020.

Looking through the eyes of a drug hunter, it is fantastic to know that, finally, fast genetic modifications no longer have to be limited to yeast systems. Indeed, CRISPR Cas9 is greatly advancing the generation of model systems, the validation of drug targets and also the identification of new targets in previously inaccessible biological systems. Even therapeutic applications are possible with the promise of correcting faulty genes in patients. Furthermore, the tool is still evolving and almost daily, the attention of the scientific community is drawn to new exciting uses of this technology. It seems that with CRISPR creativity has no limits.

The CRISPR Cas9 system is a molecular scissor with the possibility of being directed to a precise location in the genome. So far, it has been shown to work very efficiently in knocking out a gene, both via cuts of major or minor part of its DNA or via insertion of stop cassettes. This process can offer a powerful tool to validate the effects of a drug or the effects of the absence of a target in a cell system. It can also boost or shut down the expression of a drug target, simulate pathologic conditions and better model a disease. Furthermore, with its handful of components, it is a versatile tool, which can cut and edit the genome to: knock out, overexpress, create base pair mutations, insert sequences at precise locations and interfere with gene expression. The fast and precise outcome, added to the speed by which this technology can perform, make it a valuable tool to add to the wide-spectrum of technologies already available.

At Evotec CRISPR Cas9 is widely used. Different licensing agreements are in place enabling use of the technology commercially. This adds important advantages when combined with the other myriad of technologies that the company offers. Evotec uses the technology to drive its target identification and validation platforms as well as aid the deconvolution of targets from phenotypic screening or in disease model generation. As an example, with the application of genome-wide CRISPR libraries into Evotec’s screening platforms, Evotec is harnessing the power of gene deletion and human cell-based disease models, to identify novel targets for downstream drug discovery programs and this helps the company’s research engine to move swiftly across the R&D Autobahn.