Fragile sites are preferential targets for integrations of MLV vectors in gene therapy

被引：39

作者：

Bester, A. C.

Schwartz, M.

Schmidt, M.

Garrigue, A.

Hacein-Bey-Abina, S.

Cavazzana-Calvo, M.

Ben-Porat, N.

Von Kalle, C.

Fischer, A.

Kerem, B. ^{[1
]}

机构：

[1] Hebrew Univ Jerusalem, Dept Genet, Silberman Life Sci Inst, IL-91904 Jerusalem, Israel

[2] Univ Freiburg, Inst Mol Med & cell Res, Dept Internal Med 1, Freiburg, Germany

[3] Lab Cytogenet, INSERM U429, Paris, France

[4] Assistance Publ Hop Paris, Dept Biotherapie, Paris, France

[5] Cincinnati Childrens Hosp, Res Fdn, Div Expt Hematol, Mol & GeneTherapy Program, Cincinnati, OH USA

[6] Hop Necker Enfants Malad, Unite Immunol & Hematol Pediat, Paris, France

来源：

GENE THERAPY | 2006年 / 13卷 / 13期

关键词：

fragile sites; viral integration; LMO2; leukemia;

D O I：

10.1038/sj.gt.3302752

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Following gene therapy of SCID-X1 using murine leukemia virus (MLV) derived vector, two patients developed leukemia owing to an activating vector integration near the LMO2 gene. We found that these integrations reside within FRA11E, a common fragile site known to correlate with chromosomal breakpoints in tumors. Further analysis showed that fragile sites attract a nonrandom number of MLV integrations, shedding light on its integration mechanism and risk-to-benefit ratio in gene therapy.

引用

页码：1057 / 1059

页数：3

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S Hacein-Bey-Abina
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C Von Kalle
A Fischer
B Kerem
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[2] Erratum: Fragile sites are preferential targets for integrations of MLV vectors in gene therapy
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