The integration characteristics of retroviral (RV) vectorsincrease the probability of interfering with the regulationof cellular genes, and account for a tangible riskof insertional mutagenesis in treated patients. To assessthe potential genotoxic risk of conventional or self-inactivating(SIN) γ-RV and lentiviral (LV) vectors independentlyfrom the biological consequences of the insertionevent, we developed a quantitative assay based on realtimereverse transcriptase—PCR on low-density arraysto evaluate alterations of gene expression in individualprimary T-cell clones. We show that the Moloney leukemiavirus long terminal repeat (LTR) enhancer has thestrongest activity in both a γ-RV and a LV vector context,while an internal cellular promoter induces deregulationof gene expression less frequently, at a shorter range andto a lower extent in both vector types. Downregulationof gene expression was observed only in the context ofLV vectors.This study indicates that insertional gene activationis determined by the characteristics of the transcriptionalregulatory elements carried by the vector, andis largely independent from the vector type or design.

Transcriptional enhancers induce insertional gene deregulation independently from the vector type and design / Maruggi, G; Porcellini, S; Facchini, G; Perna, Sk; Cattoglio, C; Sartori, D; Ambrosi, A; Schambach, A; Baum, C; Bonini, C; Bovolenta, C; Mavilio, Fulvio; Recchia, Alessandra. - In: MOLECULAR THERAPY. - ISSN 1525-0016. - STAMPA. - 17:5(2009), pp. 851-856. [10.1038/mt.2009.51]

Transcriptional enhancers induce insertional gene deregulation independently from the vector type and design

MAVILIO, Fulvio;RECCHIA, Alessandra
2009

Abstract

The integration characteristics of retroviral (RV) vectorsincrease the probability of interfering with the regulationof cellular genes, and account for a tangible riskof insertional mutagenesis in treated patients. To assessthe potential genotoxic risk of conventional or self-inactivating(SIN) γ-RV and lentiviral (LV) vectors independentlyfrom the biological consequences of the insertionevent, we developed a quantitative assay based on realtimereverse transcriptase—PCR on low-density arraysto evaluate alterations of gene expression in individualprimary T-cell clones. We show that the Moloney leukemiavirus long terminal repeat (LTR) enhancer has thestrongest activity in both a γ-RV and a LV vector context,while an internal cellular promoter induces deregulationof gene expression less frequently, at a shorter range andto a lower extent in both vector types. Downregulationof gene expression was observed only in the context ofLV vectors.This study indicates that insertional gene activationis determined by the characteristics of the transcriptionalregulatory elements carried by the vector, andis largely independent from the vector type or design.
2009
17
5
851
856
Transcriptional enhancers induce insertional gene deregulation independently from the vector type and design / Maruggi, G; Porcellini, S; Facchini, G; Perna, Sk; Cattoglio, C; Sartori, D; Ambrosi, A; Schambach, A; Baum, C; Bonini, C; Bovolenta, C; Mavilio, Fulvio; Recchia, Alessandra. - In: MOLECULAR THERAPY. - ISSN 1525-0016. - STAMPA. - 17:5(2009), pp. 851-856. [10.1038/mt.2009.51]
Maruggi, G; Porcellini, S; Facchini, G; Perna, Sk; Cattoglio, C; Sartori, D; Ambrosi, A; Schambach, A; Baum, C; Bonini, C; Bovolenta, C; Mavilio, Fulv...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/607935
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