title: Treating Immunodeficiency through HSC Gene Therapy.
abstract: Haematopoietic stem cell (HSC) gene therapy has been successfully employed as a therapeutic option to treat specific inherited immune deficiencies, including severe combined immune deficiencies (SCID) over the past two decades. Initial clinical trials using first-generation gamma-retroviral vectors to transfer corrective DNA demonstrated clinical benefit for patients, but were associated with leukemogenesis in a number of cases. Safer vectors have since been developed, affording comparable efficacy with an improved biosafety profile. These vectors are now in Phase I/II clinical trials for a number of immune disorders with more preclinical studies underway. Targeted gene editing allowing precise DNA correction via platforms such as ZFNs, TALENs and CRISPR/Cas9 may now offer promising strategies to improve the safety and efficacy of gene therapy in the future.
authors.affiliation: Molecular and Cellular Immunology Section, UCL Institute of Child Health, London, UK; Department of Paediatric Immunology, Great Ormond Street Hospital, London, UK.
authors.forename: Claire
authors.initials: C
authors.lastname: Booth
authors.affiliation: Molecular and Cellular Immunology Section, UCL Institute of Child Health, London, UK; Department of Paediatric Immunology, Great Ormond Street Hospital, London, UK.
authors.forename: H Bobby
authors.initials: HB
authors.lastname: Gaspar
authors.affiliation: Molecular and Cellular Immunology Section, UCL Institute of Child Health, London, UK; Department of Paediatric Immunology, Great Ormond Street Hospital, London, UK. Electronic address: a.thrasher@ucl.ac.uk.
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Thrasher
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000175:diagnosis / Q000209:etiology* / Q000628:therapy*; D016086:Lentivirus / Q000235:genetics; D052416:Targeted Gene Repair / Q000379:methods; D014161:Transduction, Genetic; D019076:Transgenes
keywords: gene therapy; lentiviral vectors; primary immunodeficiency