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

Details

Serval ID
serval:BIB_DE48288DB40E
Type
Article: article from journal or magazin.
Collection
Publications
Title
Gene therapy model of X-linked severe combined immunodeficiency using a modified foamy virus vector
Journal
PLoS One
Author(s)
Horino S., Uchiyama T., So T., Nagashima H., Sun S. L., Sato M., Asao A., Haji Y., Sasahara Y., Candotti F., Tsuchiya S., Kure S., Sugamura K., Ishii N.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Publication state
Published
Issued date
2013
Volume
8
Number
8
Pages
e71594
Language
english
Notes
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
eng
Research Support, Non-U.S. Gov't
PLoS One. 2013 Aug 21;8(8):e71594. doi: 10.1371/journal.pone.0071594. eCollection 2013.
Abstract
X-linked severe combined immunodeficiency (SCID-X1) is an inherited genetic immunodeficiency associated with mutations in the common cytokine receptor gamma chain (gammac) 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 gammac 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 gammac. 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 gammac-knockout (gammac-KO) mice were infected with the FV vector and transplanted into gammac-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.
Keywords
Animals, B-Lymphocytes/cytology, Disease Models, Animal, Female, Gene Transfer Techniques, Genetic Therapy/methods, *Genetic Vectors, Humans, Interleukin Receptor Common gamma Subunit/genetics, Killer Cells, Natural/cytology, Male, Mice, Mice, Knockout, Mice, SCID, Phosphorylation, Plasmids/metabolism, Polymerase Chain Reaction, Spumavirus/*genetics, T-Lymphocytes/cytology, X-Linked Combined Immunodeficiency Diseases/genetics/immunology/*therapy
Pubmed
Open Access
Yes
Create date
01/11/2017 11:29
Last modification date
20/08/2019 17:02
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