title: New frontiers in the therapy of primary immunodeficiency: From gene addition to gene editing.
abstract: The most severe primary immune deficiency diseases (PIDs) have been successfully treated with allogeneic hematopoietic stem cell transplantation for more than 4 decades. However, such transplantations have the best outcomes when there is a well-matched donor available because immune complications, such as graft-versus-host disease, are greater without a matched sibling donor. Gene therapy has been developed as a method to perform autologous transplantations of a patient's own stem cells that are genetically corrected. Through an iterative bench-to-bedside-and-back process, methods to efficiently add new copies of the relevant gene to hematopoietic stem cells have led to safe and effective treatments for several PIDs, including forms of severe combined immune deficiency, Wiskott-Aldrich syndrome, and chronic granulomatous disease. New methods for gene editing might allow additional PIDs to be treated by gene therapy because they will allow the endogenous gene to be repaired and expressed under its native regulatory elements, which are essential for genes involved in cell processes of signaling, activation, and proliferation. Gene therapy is providing exciting new treatment options for patients with PIDs, and advances are sure to continue.
authors.affiliation: Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, Calif; Department of Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, Calif; Eli & Edythe Broad Center of Stem Cell Research & Regenerative Medicine, David Geffen School of Medicine, University of California, Los Angeles, Calif; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Calif. Electronic address: dkohn1@mednet.ucla.edu.
authors.forename: Donald B
authors.initials: DB
authors.lastname: Kohn
authors.affiliation: Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, Calif.
authors.forename: Caroline Y
authors.initials: CY
authors.lastname: Kuo
mesh_terms: D000818:Animals; D000072669:Gene Editing; D015316:Genetic Therapy; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000628:therapy*
keywords: CRISPR/Cas9; Hematopoietic stem cell transplantation; gammaretroviral vector; gene editing; lentiviral vector; site-specific endonuclease; zinc finger nuclease