CRISPR/Cas9: a historical and chemical biology perspective of targeted genome engineering.

The CRISPR-Cas9 system has revolutionized the process of making changes to the DNA sequence of organisms. Relying on a simplistic model of RNA guided DNA binding and cleavage, this molecular toolbox has found application in nearly every branch of biological sciences. The story of CRISPR-Cas9 is one of discovery and development where a component of bacterial adaptive immunity has been harnessed to address important biological questions using significant inputs from physicochemical structure-function studies. In this review, we trace the evolution of CRISPR-Cas9 from its predecessor genome editing tools and document its current status with an emphasis on chemical biology aspects of modulating its activity to generate a potent tool for gene therapy applications.