Fragile Sites Are Preferential Targets for Integrations of MLV Vectors in Gene Therapy

Overview

Journal Gene Ther

Date 2006 Mar 3

PMID 16511518

Citations 23

Authors

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

Affiliations

Soon will be listed here.

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.

Citing Articles

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Impaired Replication Timing Promotes Tissue-Specific Expression of Common Fragile Sites.

Maccaroni K, Balzano E, Mirimao F, Giunta S, Pelliccia F Genes (Basel). 2020; 11(3).

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Detours to Replication: Functions of Specialized DNA Polymerases during Oncogene-induced Replication Stress.

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Gene Electrotransfer: A Mechanistic Perspective.

Rosazza C, Haberl Meglic S, Zumbusch A, Rols M, Miklavcic D Curr Gene Ther. 2016; 16(2):98-129.

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Interplay between genetic and epigenetic factors governs common fragile site instability in cancer.

Ozeri-Galai E, Tur-Sinai M, Bester A, Kerem B Cell Mol Life Sci. 2014; 71(23):4495-506.

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