1:Fundación para la Investigación Biosanitaria de Andalucía Oriental (FIBAO); 2:GENyO- Centro de Genomica e Investigacion Oncologica: Pfizer / Universidad de Granada / Junta de Andalucia

The therapeutic power of gene modification is a clinical reality in 2022. Not long ago, harnessing the perils of genotoxicity and miscarried ectopic expression of curative genes from viral vectors were major concerns in the field. However, pioneer works using nucleases in mammals three decades ago inspired emerging technologies to exploit DNA repair mechanisms in favour of a safer and more accurate approaches.

Genome editing allows to stimulate targeted DNA addition, to alter gene expression and/or to resource on the host cell promoters to drive the expression of corrective genes. Modular and programable nucleases are bringing gene modification down to nucleotide precision. Hence, its use is widespread from disease modelling to clinical trials. Therapeutic gene editing features tailored DNA modifications and is based on the use of modular or programable nucleases allowing to back-engineer single-nucleotide mutations or to stimulate safe-harbour targeted insertion of medicinal transgenes.

In this introduction to gene editing, we review nuclease-driven approaches, how many of these tools have reach clinical maturity, and how there is still room for growth in the field of medical gene editing.