Comparison of Five Retrovirus Vectors Containing the Human IL-2 Receptor γ Chain Gene for Their Ability to Restore T and B Lymphocytes in the X-Linked Severe Combined Immunodeficiency Mouse Model

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• 作者：Avilé ; s Mendoza ; Guillermo J. ; Seidel ; Nancy E. ; Otsu ; Makoto ; Anderson ; Stacie M. ; et. al.
• 刊名：Molecular Therapy
• 出版年：2001
• 出版时间：April, 2001
• 年：2001
• 卷：3
• 期：4
• 页码：565-573
• 全文大小：302 K

文摘

X-linked severe combined immunodeficiency (XSCID) is caused by mutations in the IL-2 receptor γ chain (IL2RG) gene, resulting in absent T lymphocytes and nonfunctional B lymphocytes. Recently T lymphocyte production and B lymphocyte function were restored in XSCID patients infused with autologous stem cells transduced with a retrovirus containing the human IL2RG cDNA. To optimize the expression of human IL2RG for future clinical trials, we compared five retroviral vectors expressing human IL2RG from different LTR enhancer–promoter elements in a mouse model. Northern and Southern blot analysis of hematopoietic tissues from repopulated mice revealed that the retroviral vector with the highest expression per copy number was MFG-S-hIL2RG, followed by MND-hIL2RG. All five vectors were capable of restoring lymphopoiesis in irradiated XSCID mice transplanted with transduced IL2RG-deficient hematopoietic stem cells. Transduction of IL2RG-deficient hematopoietic stem cells with all five vectors restored T lymphopoiesis in transplanted stem cell-deficient W/W^v mouse recipients. However, only XSCID stem cells transduced with the MFG-S-hIL2RG vector generated B lymphocytes in W/W^v mice. We conclude that the MFG-S-hIL2RG vector provides the best opportunity for in vivo selection and development of B and T lymphocytes for human XSCID gene therapy.