Gene therapy model of X-linked severe combined immunodeficiency using a modified foamy virus vector.
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...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3749225?pdf=render |
| _version_ | 1818487134314561536 |
|---|---|
| author | Satoshi Horino Toru Uchiyama Takanori So Hiroyuki Nagashima Shu-Lan Sun Miki Sato Atsuko Asao Yoichi Haji Yoji Sasahara Fabio Candotti Shigeru Tsuchiya Shigeo Kure Kazuo Sugamura Naoto Ishii |
| author_facet | Satoshi Horino Toru Uchiyama Takanori So Hiroyuki Nagashima Shu-Lan Sun Miki Sato Atsuko Asao Yoichi Haji Yoji Sasahara Fabio Candotti Shigeru Tsuchiya Shigeo Kure Kazuo Sugamura Naoto Ishii |
| author_sort | Satoshi Horino |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T16:33:17Z |
| format | Article |
| id | doaj.art-cc6e14ba193741ca86d06061430ec035 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T16:33:17Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-cc6e14ba193741ca86d06061430ec0352022-12-22T01:41:30ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0188e7159410.1371/journal.pone.0071594Gene therapy model of X-linked severe combined immunodeficiency using a modified foamy virus vector.Satoshi HorinoToru UchiyamaTakanori SoHiroyuki NagashimaShu-Lan SunMiki SatoAtsuko AsaoYoichi HajiYoji SasaharaFabio CandottiShigeru TsuchiyaShigeo KureKazuo SugamuraNaoto IshiiX-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.http://europepmc.org/articles/PMC3749225?pdf=render |
| spellingShingle | Satoshi Horino Toru Uchiyama Takanori So Hiroyuki Nagashima Shu-Lan Sun Miki Sato Atsuko Asao Yoichi Haji Yoji Sasahara Fabio Candotti Shigeru Tsuchiya Shigeo Kure Kazuo Sugamura Naoto Ishii Gene therapy model of X-linked severe combined immunodeficiency using a modified foamy virus vector. PLoS ONE |
| title | Gene therapy model of X-linked severe combined immunodeficiency using a modified foamy virus vector. |
| title_full | Gene therapy model of X-linked severe combined immunodeficiency using a modified foamy virus vector. |
| title_fullStr | Gene therapy model of X-linked severe combined immunodeficiency using a modified foamy virus vector. |
| title_full_unstemmed | Gene therapy model of X-linked severe combined immunodeficiency using a modified foamy virus vector. |
| title_short | Gene therapy model of X-linked severe combined immunodeficiency using a modified foamy virus vector. |
| title_sort | gene therapy model of x linked severe combined immunodeficiency using a modified foamy virus vector |
| url | http://europepmc.org/articles/PMC3749225?pdf=render |
| work_keys_str_mv | AT satoshihorino genetherapymodelofxlinkedseverecombinedimmunodeficiencyusingamodifiedfoamyvirusvector AT toruuchiyama genetherapymodelofxlinkedseverecombinedimmunodeficiencyusingamodifiedfoamyvirusvector AT takanoriso genetherapymodelofxlinkedseverecombinedimmunodeficiencyusingamodifiedfoamyvirusvector AT hiroyukinagashima genetherapymodelofxlinkedseverecombinedimmunodeficiencyusingamodifiedfoamyvirusvector AT shulansun genetherapymodelofxlinkedseverecombinedimmunodeficiencyusingamodifiedfoamyvirusvector AT mikisato genetherapymodelofxlinkedseverecombinedimmunodeficiencyusingamodifiedfoamyvirusvector AT atsukoasao genetherapymodelofxlinkedseverecombinedimmunodeficiencyusingamodifiedfoamyvirusvector AT yoichihaji genetherapymodelofxlinkedseverecombinedimmunodeficiencyusingamodifiedfoamyvirusvector AT yojisasahara genetherapymodelofxlinkedseverecombinedimmunodeficiencyusingamodifiedfoamyvirusvector AT fabiocandotti genetherapymodelofxlinkedseverecombinedimmunodeficiencyusingamodifiedfoamyvirusvector AT shigerutsuchiya genetherapymodelofxlinkedseverecombinedimmunodeficiencyusingamodifiedfoamyvirusvector AT shigeokure genetherapymodelofxlinkedseverecombinedimmunodeficiencyusingamodifiedfoamyvirusvector AT kazuosugamura genetherapymodelofxlinkedseverecombinedimmunodeficiencyusingamodifiedfoamyvirusvector AT naotoishii genetherapymodelofxlinkedseverecombinedimmunodeficiencyusingamodifiedfoamyvirusvector |