PMID: 16511518DOI: 10.1038/sj.gt.3302752Mar 3, 2006Paper
Fragile sites are preferential targets for integrations of MLV vectors in gene therapy
Gene Therapy
Assaf C BesterBatsheva 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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