title: Lessons Learned from Two Decades of Clinical Trial Experience in Gene Therapy for Fanconi Anemia.
abstract: Allogeneic hematopoietic stem cell transplantation is the only curative treatment for patients with the non-malignant bone marrow failure syndrome called Fanconi anemia (FA). However, early and late complications associated with this approach underscore the need for alternative treatments. Gene therapy approaches aiming to correct the genetic defect in the patient's own hematopoietic stem cells remain the most promising strategy to overcome FA-associated bone marrow failure. Yet, despite more than two decades of clinical research, a therapeutic "success" has not yet been achieved. Here we review the clinical trials conducted to date and highlight the unique features of FA revealed by these studies. These features render FA the "holy grail" of hematopoietic stem cell gene therapy approaches, and identify the future steps required to achieve clinical success in this rare disease.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Adair
authors.forename: Julian
authors.initials: J
authors.lastname: Sevilla
authors.forename: Cristina Diaz de
authors.initials: CD
authors.lastname: Heredia
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Becker
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, United States.
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Kiem
authors.affiliation: Centro de Investigaciones Energeticas, Medioambientales y Tecnologicas (CIEMAT) Madrid, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Bueren
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D005199:Fanconi Anemia / Q000235:genetics / Q000628:therapy*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D014184:Transplantation, Homologous
keywords: Bone marrow failure; Clinical trials; Fanconi anemia; Gene therapy; Stem cells; Viral vectors