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.