Foamy virus vector-mediated gene transfer into long-term HSC in the gene therapy for primary immunodeficiencies.

2014 Fiscal Year Final Research Report

• Project/Area Number: 25860836
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: National Research Institute for Child Health and Development
• Principal Investigator: UCHIYAMA TORU 独立行政法人国立成育医療研究センター, 成育遺伝研究部, 室長 (10436107)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: FVベクター / X連鎖重症複合免疫不全症 / 遺伝子治療

Outline of Final Research Achievements

Using Foamy virus-based (FV) vector, we have established the gene transfer system for X-linked severe combined immunodeficiency (X-SCID). We constructed FV vector containing human γc under the control of A2UCOE for stable gene expression, and transduced the bone marrow cells from X-SCID mice. Gene transduced cells were transplanted into NOD/SCID-γc null mice, which provided high level of engraftment of hematopoietic cells. In transplanted mice, splenic T cells showed the improvement in proliferation and IL-2 production in response to anti-CD3 stimulation, and serum levels of IgM, IgA and IgG were also elevated. These results revealed the functional reconstitution of immune system. Analysis of vector integration demonstrated that FV integration sites were slightly less likely to be located within or near transcriptional start sites than retroviral vector (RV) integration sites. These data suggest that FV vector is a safer system than RV vector in stem cell gene therapy for X-SCID.

Free Research Field

遺伝子治療、血液、免疫