title: Functional correction of fanconi anemia group C hematopoietic cells by the use of a novel lentiviral vector.
abstract: Lentiviral vectors transduce nondividing hematopoietic cells more efficiently than other currently available vector systems. Here we report the results of human hematopoietic cell gene transfer using lentiviral vectors based upon human immunodeficiency virus (HIV-1) and equine infectious anemia virus (EIAV). EIAV is a nonprimate lentivirus and is severely restricted in its host range to horses and closely related equines. We employed the EIAV vector system to test for gene transfer to human Fanconi anemia (FA) hematopoietic cells by comparison with HIV-1- and Moloney murine leukemia virus-based systems. Fanconi anemia is characterized by bone marrow failure secondary to stem cell dysfunction. Fanconi anemia group C EBV-transformed lymphoblasts were transduced with all three viral vectors. Phenotypic correction of FA cells, as measured by mitomycin C drug resistance, was observed with a similar efficiency in all vector systems. This is the first description of lentiviral correction of FA cells and suggests that lentiviral vectors may be useful for FA gene transfer.
authors.affiliation: UNC Gene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
authors.forename: K
authors.initials: K
authors.lastname: Yamada
authors.forename: J C
authors.initials: JC
authors.lastname: Olsen
authors.forename: M
authors.initials: M
authors.lastname: Patel
authors.forename: K W
authors.initials: KW
authors.lastname: Rao
authors.forename: C E
authors.initials: CE
authors.lastname: Walsh
mesh_terms: D002453:Cell Cycle; D018797:Cell Cycle Proteins; D002460:Cell Line; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005199:Fanconi Anemia / Q000235:genetics* / Q000628:therapy*; D052218:Fanconi Anemia Complementation Group C Protein; D051856:Fanconi Anemia Complementation Group Proteins; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D004860:Infectious Anemia Virus, Equine / Q000235:genetics; D007700:Kinetics; D016086:Lentivirus / Q000235:genetics*; D008214:Lymphocytes / Q000378:metabolism; D016685:Mitomycin / Q000494:pharmacology; D008957:Models, Genetic; D009687:Nuclear Proteins; D010641:Phenotype; D010957:Plasmids / Q000378:metabolism; D011506:Proteins / Q000235:genetics*; D019076:Transgenes
chemical_list: D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C497651:FANCC protein, human; D052218:Fanconi Anemia Complementation Group C Protein; D051856:Fanconi Anemia Complementation Group Proteins; D009687:Nuclear Proteins; D011506:Proteins; D016685:Mitomycin