title: Establishment of modified retroviral vector targeting X-linked severe combined immunodeficiency.
abstract: Gene therapy targeting hematopoietic stem cells has been proposed as a potential therapy for numerous genetic disorders affecting hematopoiesis. Moloney murine leukemia retroviral vectors are now widely used for clinical gene transfer into hematopoietic progenitors and progeny. However, maintaining expression of therapeutic genes inserted via moloney murine leukemia virus (MoMLV)-based vectors has proven to be more difficult than previously expected. In this study, an MND-IL-2R vector containing IL-2Rc gamma cDNA to treat X-linked severe combined immunodeficiency (X-SCID) was constructed from an MND vector that was modified by substituting the myeloproliferative sarcoma virus (MPSV) enhancer for that of MoMLV, deleting the negative control region located in the long terminal repeat (LTR) as an enhancer, and replacing the primer binding site (PBS) of MoMLV with the PBS of the endogenous murine retrovirus dl587rev. This vector was transduced into human CD34 + progenitor cells with comparable efficiency to that of the MoMLV-based vector. The use of this newly created vector may be advantageous for gene therapy of X-SCID.
authors.affiliation: Department of Pediatrics, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan.
authors.forename: Cai Ling
authors.initials: CL
authors.lastname: Zhi
authors.forename: Makoto
authors.initials: M
authors.lastname: Migita
authors.forename: Jun
authors.initials: J
authors.lastname: Hayakawa
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Fukunaga
mesh_terms: D018952:Antigens, CD34; D002478:Cells, Cultured; D004742:Enhancer Elements, Genetic; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics / Q000627:therapeutic use*; D006412:Hematopoietic Stem Cells / Q000821:virology*; D006801:Humans; D008979:Moloney murine leukemia virus / Q000235:genetics*; D008980:Moloney murine sarcoma virus / Q000235:genetics; D016511:Severe Combined Immunodeficiency / Q000628:therapy*; D020079:Terminal Repeat Sequences / Q000235:genetics; D014161:Transduction, Genetic
chemical_list: D018952:Antigens, CD34