title: Gene therapy for fanconi anemia.
abstract: Fanconi anemia is a hereditary syndrome of bone marrow failure, congenital anomalies, and a predisposition to malignancy. Most patients die from bone marrow failure. Cells from patients display a heightened sensitivity to DNA cross-linking agents with increased chromosomal breakage and increased cytotoxicity. Bone marrow from patients with Fanconi anemia have decreased numbers of hematopoietic progenitors when grown in culture. Transfer of the normal Fanconi anemia cDNA into cells from patients corrects the laboratory abnormalities, suggesting that gene transfer may prevent or reverse the bone marrow failure. Advances in gene transfer into human hematopoietic cells make this approach seem feasible. However, decreased numbers of stem cell targets may represent a significant obstacle. In addition, new insights on potential toxicities related to gene transfer have heightened a cautious approach. Fanconi anemia represents a prototype disorder for gene therapy and highlights the difficulties in adapting this technology to human disease.
authors.affiliation: Pediatric Hematology/Oncology, James Whitcomb Riley Hospital for Children, 702 Barnhill Drive, Indianapolis, IN 46202, USA. jcroop@iupui.edu
authors.forename: James M
authors.initials: JM
authors.lastname: Croop
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D005199:Fanconi Anemia / Q000628:therapy*; D052217:Fanconi Anemia Complementation Group A Protein; D052236:Fanconi Anemia Complementation Group D2 Protein; D052219:Fanconi Anemia Complementation Group F Protein; D052241:Fanconi Anemia Complementation Group G Protein; D051856:Fanconi Anemia Complementation Group Proteins; D015316:Genetic Therapy / Q000379:methods*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins; D011506:Proteins / Q000235:genetics; D016601:RNA-Binding Proteins
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C498471:FANCA protein, human; C499905:FANCD2 protein, human; C499901:FANCF protein, human; C499909:FANCG protein, human; D052217:Fanconi Anemia Complementation Group A Protein; D052236:Fanconi Anemia Complementation Group D2 Protein; D052219:Fanconi Anemia Complementation Group F Protein; D052241:Fanconi Anemia Complementation Group G Protein; D051856:Fanconi Anemia Complementation Group Proteins; D009687:Nuclear Proteins; D011506:Proteins; D016601:RNA-Binding Proteins