Retroviral-mediated transfer and expression of the common gamma chain into human hematopoietic progenitors.
The common gamma chain (gammac) of cytokine receptors is mutated in X-linked severe combined immunodeficiency, a lethal disorder characterized by the absence of both humoral and cellular immune defenses. Allogeneic bone marrow transplantation from HLA-identical siblings usually results in complete reconstitution of the immune system and is the current treatment of choice. Genetic correction and reinfusion of autologous hematopoietic stem cells represents an alternative therapeutic approach for those patients who lack suitable marrow donors. In this study, we show that retroviral-mediated transfer of the gammac gene results in efficient expression in CD34+ cells and high transduction rate of colony-forming progenitors.
Candotti
F
F
Clinical Gene Therapy Branch, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA. fabio@nhgri.nih.gov
Onodera
M
M
Knazek
R A
RA
Blaese
R M
RM
D018952:Antigens, CD34 / Q000032:analysis; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004351:Drug Resistance / Q000235:genetics; D015870:Gene Expression; D018014:Gene Transfer Techniques; D008040:Genetic Linkage; D005865:Gestational Age; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000196:embryology; D009154:Mutation; D009355:Neomycin; D018123:Receptors, Interleukin / Q000235:genetics*; D012190:Retroviridae / Q000235:genetics*; D016511:Severe Combined Immunodeficiency / Q000235:genetics; D014960:X Chromosome
D018952:Antigens, CD34; D018123:Receptors, Interleukin; D009355:Neomycin