Genome editing: the road of CRISPR/Cas9 from bench to clinic

Molecular scissors engineered for site-specific modification of the genome hold great promise for effective functional analyses of genes, genomes and epigenomes and could improve our understanding of the molecular underpinnings of disease states and facilitate novel therapeutic applications. Several platforms for molecular scissors that enable targeted genome engineering have been developed, including zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and, most recently, clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated-9 (Cas9). The CRISPR/Cas9 system’s simplicity, facile engineering and amenability to multiplexing make it the system of choice for many applications. CRISPR/Cas9 has been used to generate disease models to study genetic diseases. Improvements are urgently needed for various aspects of the CRISPR/Cas9 system, including the system’s precision, delivery and control over the outcome of the repair process. Here, we discuss the current status of genome engineering and its implications for the future of biological research and gene therapy. Improved methods for breaking and editing the genome will revolutionize genomic and biological research. Genome editing techniques known as ‘molecular scissors’ enable a cell's genome to be cut at a specific location, allowing genes to be removed, added or mutated as desired. These techniques help researchers understand the molecular mechanisms underpinning multiple diseases, and could lead to novel gene therapies for conditions such as Alzheimer's disease and HIV. Magdy Mahfouz and Ayman Eid at King Abdullah University of Science and Technology in Saudi Arabia reviewed the current status of several genome editing techniques and concluded that the newest system, ‘clustered regularly interspaced palindromic repeats’ (CRISPR/Cas9), holds the greatest potential to transform the field. The researchers call for further improvements in CRISPR/Cas9 to ensure that precision, delivery and control are refined in order to limit side-effects.