Gene Therapy Model of X-linked Severe Combined Immunodeficiency Using a Modified Foamy Virus Vector

作者：Horino Satoshi; Uchiyama Toru; So Takanori; Nagashima Hiroyuki; Sun Shu lan; Sato Miki; Asao Atsuko; Haji Yoichi; Sasahara Yoji; Candotti Fabio; Tsuchiya Shigeru; Kure Shigeo; Sugamura Kazuo; Ishii Naoto^*

来源：PLos One, 2013, 8(8): e71594.

DOI：10.1371/journal.pone.0071594

X-linked severe combined immunodeficiency (SCID-X1) is an inherited genetic immunodeficiency associated with mutations in the common cytokine receptor gamma chain (gamma c) 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 gamma c 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 gamma c. 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 gamma c-knockout (gamma c-KO) mice were infected with the FV vector and transplanted into gamma c-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.

• 出版日期2013-8-21