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

Giulietta Maruggi, Simona Porcellini, Giulia Facchini, Serena K. Perna, Claudia Cattoglio, Daniela Sartori, Alessandro Ambrosi, Axel Schambach, Christopher Baum, Chiara Bonini, Chiara Bovolenta, Fulvio Mavilio, Alessandra Recchia

Research output: Contribution to journalArticle

Abstract

The integration characteristics of retroviral (RV) vectors increase the probability of interfering with the regulation of cellular genes, and account for a tangible risk of insertional mutagenesis in treated patients. To assess the potential genotoxic risk of conventional or self-inactivating (SIN) γ-RV and lentiviral (LV) vectors independently from the biological consequences of the insertion event, we developed a quantitative assay based on real-time reverse transcriptase-PCR on low-density arrays to evaluate alterations of gene expression in individual primary T-cell clones. We show that the Moloney leukemia virus long terminal repeat (LTR) enhancer has the strongest activity in both a γ-RV and a LV vector context, while an internal cellular promoter induces deregulation of gene expression less frequently, at a shorter range and to a lower extent in both vector types. Downregulation of gene expression was observed only in the context of LV vectors. This study indicates that insertional gene activation is determined by the characteristics of the transcriptional regulatory elements carried by the vector, and is largely independent from the vector type or design.

Original languageEnglish
Pages (from-to)851-856
Number of pages6
JournalMolecular Therapy
Volume17
Issue number5
DOIs
Publication statusPublished - 2009

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Genetics
  • Drug Discovery
  • Pharmacology

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  • Cite this

    Maruggi, G., Porcellini, S., Facchini, G., Perna, S. K., Cattoglio, C., Sartori, D., Ambrosi, A., Schambach, A., Baum, C., Bonini, C., Bovolenta, C., Mavilio, F., & Recchia, A. (2009). Transcriptional enhancers induce insertional gene deregulation independently from the vector type and design. Molecular Therapy, 17(5), 851-856. https://doi.org/10.1038/mt.2009.51