AUTHOR=Blattner Georges , Cavazza Alessia , Thrasher Adrian J. , Turchiano Giandomenico TITLE=Gene Editing and Genotoxicity: Targeting the Off-Targets JOURNAL=Frontiers in Genome Editing VOLUME=2 YEAR=2020 URL=https://www.frontiersin.org/journals/genome-editing/articles/10.3389/fgeed.2020.613252 DOI=10.3389/fgeed.2020.613252 ISSN=2673-3439 ABSTRACT=

Gene editing technologies show great promise for application to human disease as a result of rapid developments in targeting tools notably based on ZFN, TALEN, and CRISPR-Cas systems. Precise modification of a DNA sequence is now possible in mature human somatic cells including stem and progenitor cells with increasing degrees of efficiency. At the same time new technologies are required to evaluate their safety and genotoxicity before widespread clinical application can be confidently implemented. A number of methodologies have now been developed in an attempt to predict expected and unexpected modifications occurring during gene editing. This review surveys the techniques currently available as state of the art, highlighting benefits and limitations, and discusses approaches that may achieve sufficient accuracy and predictability for application in clinical settings.