title: Genome editing in pluripotent stem cells: research and therapeutic applications.
abstract: Recent progress in human pluripotent stem cell (hPSC) and genome editing technologies has opened up new avenues for the investigation of human biology in health and disease as well as the development of therapeutic applications. Gene editing approaches with programmable nucleases have been successfully established in hPSCs and applied to study gene function, develop novel animal models and perform genetic and chemical screens. Several studies now show the successful editing of disease-linked alleles in somatic and patient-derived induced pluripotent stem cells (iPSCs) as well as in animal models. Importantly, initial clinical trials have shown the safety of programmable nucleases for ex vivo somatic gene therapy. In this context, the unlimited proliferation potential and the pluripotent properties of iPSCs may offer advantages for gene targeting approaches. However, many technical and safety issues still need to be addressed before genome-edited iPSCs are translated into the clinical setting. Here, we provide an overview of the available genome editing systems and discuss opportunities and perspectives for their application in basic research and clinical practice, with a particular focus on hPSC based research and gene therapy approaches. Finally, we discuss recent research on human germline genome editing and its social and ethical implications.
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE) Tübingen within the Helmholtz Association, Tübingen, Germany; Hertie Institute for Clinical Brain Research, University of Tübingen, Germany. Electronic address: michela.deleidi@dzne.de.
authors.forename: Michela
authors.initials: M
authors.lastname: Deleidi
authors.affiliation: Department of Microbiology and Immunology, School of Medicine and Biomedical Sciences, University at Buffalo, New York, USA.
authors.forename: Cong
authors.initials: C
authors.lastname: Yu
mesh_terms: D000483:Alleles; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D003851:Deoxyribonucleases / Q000378:metabolism; D000072669:Gene Editing; D015316:Genetic Therapy / Q000379:methods; D015894:Genome, Human; D059765:Homologous Recombination; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology; D009154:Mutation; D039904:Pluripotent Stem Cells / Q000166:cytology*
chemical_list: D003851:Deoxyribonucleases
keywords: Disease modeling; Gene editing; Gene therapy; Induced pluripotent stem cells; Programmable nucleases