CRISPR/Cas9: The new era of gene therapy

The Clustered Regularly Interspaced Short Palindromic Repeats/CRISPRassociated protein (CRISPR/Cas) system is present in many Bacteria and in almost all Archaea and functions in those organisms as a defense mechanism against invading viruses and plasmids. Since the function and the working mechanism of the bacterial CRISPR/Cas system were elucidated in 2007, and researchers realized its potential as a gene-editing tool in 2012, it quickly became a widely used tool to generate mutations in cells, cell lines, and various model organisms. Applications such as improvement of disease resistance of economic plants, enhancement of muscle growth, or litter size in livestock are already becoming common practice. More recently, its application to repair genetic mutations has been explored in human cells and cell lines, and currently, the first clinical trials are underway in which the CRISPR/Cas9 system is applied to cure patients from various diseases. When looking at the timeline, it is clear that the CRISPR/Cas9 system has revolutionized genome engineering in less than a decade and may well be the most versatile genome engineering tool available. Here we review the origin and function of the CRISPR/Cas9 system, its working mechanism, and its use in various model organisms. In addition, pitfalls of the method are discussed, as well as the currently running and planned clinical trials. The objectives of this review are: first, to inform readers of the working mechanism of this new technique and how it is currently used to facilitate research in model organisms and to improve the profitability of livestock and economic plants. And second, to provide insight into the application of this technique in the treatment of disease in humans.(C) 2020 The Authors. Published by IASE.