Genome Editing in Stem Cells

Progress in the derivation, expansion and differentiation of human embryonic stem cells in vitro has led to the development of a valuable platform for studying disease as well as providing an inexhaustible resource for cell replacement therapies. Targeted modification of stem cells utilising synthetic nucleases provides a means to genetically alter the genome in an efficient, site-specific manner. Editing with this approach offers a possibility to improve disease modelling in both patient-derived induced pluripotent stem cells (iPSCs) and embryonic and adult stem cells. It is possible that in the future, patients with monogenic diseases could be treated or cured by transplantation of autologous cells that have been altered to have the corrected genetic sequence. Currently, genetic modification of stem cells in vitro is most often achieved using siRNA or viral transduction; however, this can result in only transient modulation or raise the possibility of insertional mutagenesis, respectively. Targeted genome editing using zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and more recently clustered regularly interspaced short palindromic repeats (CRISPRs)/CRISPR-associated protein 9 (Cas9) have been developed to overcome the drawbacks of gene transfer. In this review, we mechanistically outline these technologies before focusing on their expanding utility within the biomedical sciences. © 2015, Springer International Publishing AG.