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

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

doi:10.1038/sj.gt.3302752

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

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

^*Corresponding author for this work

Department of Genetics

Research output: Contribution to journal › Article › peer-review

45 Scopus citations

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.

Original language	English
Pages (from-to)	1057-1059
Number of pages	3
Journal	Gene Therapy
Volume	13
Issue number	13
DOIs	https://doi.org/10.1038/sj.gt.3302752
State	Published - Jul 2006

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Fragile sites
LMO2
Leukemia
Viral integration

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10.1038/sj.gt.3302752

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title = "Fragile sites are preferential targets for integrations of MLV vectors in gene therapy",

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.",

keywords = "Fragile sites, LMO2, Leukemia, Viral integration",

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AU - Bester, A. C.

AU - Schwartz, M.

AU - Schmidt, M.

AU - Garrigue, A.

AU - Hacein-Bey-Abina, S.

AU - Cavazzana-Calvo, M.

AU - Ben-Porat, N.

AU - Von Kalle, C.

AU - Fischer, A.

AU - Kerem, B.

PY - 2006/7

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N2 - 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.

AB - 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.

KW - Fragile sites

KW - LMO2

KW - Leukemia

KW - Viral integration

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VL - 13

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EP - 1059

JO - Gene Therapy

JF - Gene Therapy

IS - 13

ER -

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

Abstract

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Keywords

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