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.
Subject(s)
Genetic Therapy/methods , Genetic Vectors/therapeutic use , Hematopoietic Stem Cells/virology , Moloney murine leukemia virus/genetics , Severe Combined Immunodeficiency/therapy , Antigens, CD34 , Cells, Cultured , Enhancer Elements, Genetic , Gene Transfer Techniques , Genetic Vectors/genetics , Humans , Moloney murine sarcoma virus/genetics , Terminal Repeat Sequences/genetics , Transduction, GeneticABSTRACT
A 7 year-old girl was admitted to our hospital with high grade fever and redness, swelling and tenderness in left neck. CT scan revealed cyst formation (4.5x3 cm) in left lobe of thyroid with swelling of surrounding lymphonodes. We diagnosed her as acute suppurative thyroiditis and treated her with intravenous antibiotics infusion and incisional drainage. After the treatment, the clinical course was uneventful. Pharyngograph revealed left piriform sinus fistula.
