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PLoS One. 2013 Aug 21;8(8):e71594. doi: 10.1371/journal.pone.0071594. eCollection 2013.

Gene therapy model of X-linked severe combined immunodeficiency using a modified foamy virus vector.

Author information

1
Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Japan ; Department of Pediatrics, Tohoku University Graduate School of Medicine, Sendai, Japan.

Abstract

X-linked severe combined immunodeficiency (SCID-X1) is an inherited genetic immunodeficiency associated with mutations in the common cytokine receptor γ chain (γc) gene, and characterized by a complete defect of T and natural killer (NK) cells. Gene therapy for SCID-X1 using conventional retroviral (RV) vectors carrying the γc gene results in the successful reconstitution of T cell immunity. However, the high incidence of vector-mediated T cell leukemia, caused by vector insertion near or within cancer-related genes has been a serious problem. In this study, we established a gene therapy model of mouse SCID-X1 using a modified foamy virus (FV) vector expressing human γc. Analysis of vector integration in a human T cell line demonstrated that the FV vector integration sites were significantly less likely to be located within or near transcriptional start sites than RV vector integration sites. To evaluate the therapeutic efficacy, bone marrow cells from γc-knockout (γc-KO) mice were infected with the FV vector and transplanted into γc-KO mice. Transplantation of the FV-treated cells resulted in the successful reconstitution of functionally active T and B cells. These data suggest that FV vectors can be effective and may be safer than conventional RV vectors for gene therapy for SCID-X1.

PMID:
23990961
PMCID:
PMC3749225
DOI:
10.1371/journal.pone.0071594
[Indexed for MEDLINE]
Free PMC Article

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