CRISPR/Cas System in Human Genetic Diseases

Abstract

Gene editing involves altering a particular sequence within an organism’s genome using gene-editing techniques. Efficiently and accurately insert, delete or replace genes to alter their genetic information and phenotypic characteristics. DNA nuclease-based gene editing technology has advanced rapidly, from the first-generation editing system ZFNs, the second-generation TALENs to the third-generation CRISPR/Cas9 system, the efficiency of gene editing has been continuously improved, the cost has been gradually reduced, and the application scope has been expanding. The new classification system categorizes CRISPR-Cas proteins into Class I and II as the two main classes. Class I encompasses several subtypes, including Type I, III, and IV, all form complexes through the coordinated function of multiple Cas proteins. While Class II includes Type II, Type V, and Type VI, which all rely on single large Cas protein to perform all response. By designing single guide RNA (sgRNA), CRISPR can be used to target any gene sequence intended to be edited, achieving the wanted therapeutic outcome in treatment of inherited genetic disease. Although potential for off-target leads to undesired genetic alterations even result in oncogenesis, CRISPR-Cas still works as powerful therapy and gene editing tool in all aspects. Future research requires us to solve off-target issue. This review systematically introduces CRISPR-Cas systems as promising therapeutic strategy towards various genetic disease, explaining molecular mechanism and classification of CRISPR and differences among them.