Literature DB >> 16511518

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

A C Bester1, M Schwartz, M Schmidt, A Garrigue, S Hacein-Bey-Abina, M Cavazzana-Calvo, N Ben-Porat, C Von Kalle, A Fischer, B Kerem.   

Abstract

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.

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Year:  2006        PMID： 16511518     DOI： 10.1038/sj.gt.3302752

Source DB:  PubMed          Journal:  Gene Ther        ISSN： 0969-7128            Impact factor:   5.250


  23 in total

Review 1.  What is (still not) known of the mechanism by which electroporation mediates gene transfer and expression in cells and tissues.

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2.  Vector integration and tumorigenesis.

Authors:  Christof von Kalle; Annette Deichmann; Manfred Schmidt
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Review 3.  Interplay between genetic and epigenetic factors governs common fragile site instability in cancer.

Authors:  Efrat Ozeri-Galai; Michal Tur-Sinai; Assaf C Bester; Batsheva Kerem
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Review 4.  Molecular characterization of common fragile sites as a strategy to discover cancer susceptibility genes.

Authors:  Larissa Savelyeva; Lena M Brueckner
Journal:  Cell Mol Life Sci       Date:  2014-09-18       Impact factor: 9.261

Review 5.  Platelets as delivery systems for disease treatments.

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6.  Role of SV40 integration site at chromosomal interval 1q21.1 in immortalized CRL2504 cells.

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7.  Integration site preference of xenotropic murine leukemia virus-related virus, a new human retrovirus associated with prostate cancer.

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Review 8.  Recent advances in gene therapy for severe congenital immunodeficiency diseases.

Authors:  Robert Sokolic; Chimene Kesserwan; Fabio Candotti
Journal:  Curr Opin Hematol       Date:  2008-07       Impact factor: 3.284

9.  Transduction of fetal mice with a feline lentiviral vector induces liver tumors which exhibit an E2F activation signature.

Authors:  Reba Condiotti; Daniel Goldenberg; Hilla Giladi; Temima Schnitzer-Perlman; Simon N Waddington; Suzanne Mk Buckley; Denise Heim; Wing Cheung; Matthew Themis; Charles Coutelle; Alina Simerzin; Emma Osejindu; Henning Wege; Michael Themis; Eithan Galun
Journal:  Mol Ther       Date:  2013-08-28       Impact factor: 11.454

10.  ATR preferentially interacts with common fragile site FRA3B and the binding requires its kinase activity in response to aphidicolin treatment.

Authors:  Cheng Wan; Atul Kulkarni; Yuh-Hwa Wang
Journal:  Mutat Res       Date:  2010-01-07       Impact factor: 2.433
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