title: Refining strategies to translate genome editing to the clinic.
abstract: Recent progress in developing programmable nucleases, such as zinc-finger nucleases, transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeat (CRISPR)-Cas nucleases, have paved the way for gene editing to enter clinical practice. This translation is a result of combining high nuclease activity with high specificity and successfully applying this technology in various preclinical disease models, including infectious disease, primary immunodeficiencies, hemoglobinopathies, hemophilia and muscular dystrophy. Several clinical gene-editing trials, both ex vivo and in vivo, have been initiated in the past 2 years, including studies that aim to knockout genes as well as to add therapeutic transgenes. Here we discuss the advances made in the gene-editing field in recent years, and specify priorities that need to be addressed to expand therapeutic genome editing to further disease entities.
authors.affiliation: Institute for Cell and Gene Therapy, Medical Center-University of Freiburg, Freiburg, Germany.|Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Freiburg, Germany.
authors.forename: Tatjana I
authors.initials: TI
authors.lastname: Cornu
authors.affiliation: Institute for Cell and Gene Therapy, Medical Center-University of Freiburg, Freiburg, Germany.|Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Freiburg, Germany.
authors.forename: Claudio
authors.initials: C
authors.lastname: Mussolino
authors.affiliation: Institute for Cell and Gene Therapy, Medical Center-University of Freiburg, Freiburg, Germany.|Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Freiburg, Germany.|University of Freiburg, Freiburg, Germany.
authors.forename: Toni
authors.identifier: http://orcid.org/0000-0002-7757-4630
authors.initials: T
authors.lastname: Cathomen
mesh_terms: D064113:CRISPR-Cas Systems; D002986:Clinical Trials as Topic; D003851:Deoxyribonucleases; D000229:Dependovirus; D000072669:Gene Editing / Q000331:legislation & jurisprudence / Q000379:methods*; D005822:Genetic Vectors; D015658:HIV Infections / Q000628:therapy*; D006453:Hemoglobinopathies / Q000628:therapy*; D006467:Hemophilia A / Q000628:therapy*; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000628:therapy*; D007938:Leukemia / Q000628:therapy; D009136:Muscular Dystrophies / Q000628:therapy*; D009369:Neoplasms / Q000628:therapy*; D000069896:Transcription Activator-Like Effector Nucleases
chemical_list: D003851:Deoxyribonucleases; D000069896:Transcription Activator-Like Effector Nucleases