Buchumschlag

Lentiviral vector common integration sites in preclinical models and a clinical trial reflect a benign integration bias and not oncogenic selection

A recent clinical trial for adrenoleukodystrophy (ALD) showed the efficacy and safety of lentiviral vector (LV) gene transfer in hematopoietic stem progenitor cells. However, several common insertion sites (CIS) were found in patients' cells, suggesting that LV integrations conferred a selectiv...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Hauptverfasser: Biffi, Alessandra (VerfasserIn) , Bartholomä, Cynthia C. (VerfasserIn) , Cesana, Daniela (VerfasserIn) , Cartier, Natalie (VerfasserIn) , Aubourg, Patrik (VerfasserIn) , Ranzani, Marco (VerfasserIn) , Cesani, Martina (VerfasserIn) , Benedicenti, Fabrizio (VerfasserIn) , Plati, Tiziana (VerfasserIn) , Rubagotti, Enrico (VerfasserIn) , Merella, Stefania (VerfasserIn) , Capotondo, Alessia (VerfasserIn) , Sgualdino, Jacopo (VerfasserIn) , Zanetti, Gianluigi (VerfasserIn) , Kalle, Christof von (VerfasserIn) , Schmidt, Manfred (VerfasserIn) , Naldini, Luigi (VerfasserIn) , Montini, Eugenio (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: May 19 2011
In: Blood
Year: 2011, Jahrgang: 117, Heft: 20, Pages: 5332-5339
ISSN:1528-0020
DOI:10.1182/blood-2010-09-306761
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1182/blood-2010-09-306761
Volltext
Verfasserangaben:Alessandra Biffi, Cynthia C. Bartolomae, Daniela Cesana, Natalie Cartier, Patrik Aubourg, Marco Ranzani, Martina Cesani, Fabrizio Benedicenti, Tiziana Plati, Enrico Rubagotti, Stefania Merella, Alessia Capotondo, Jacopo Sgualdino, Gianluigi Zanetti, Christof von Kalle, Manfred Schmidt, Luigi Naldini, and Eugenio Montini
Beschreibung
Zusammenfassung:A recent clinical trial for adrenoleukodystrophy (ALD) showed the efficacy and safety of lentiviral vector (LV) gene transfer in hematopoietic stem progenitor cells. However, several common insertion sites (CIS) were found in patients' cells, suggesting that LV integrations conferred a selective advantage. We performed high-throughput LV integration site analysis on human hematopoietic stem progenitor cells engrafted in immunodeficient mice and found the same CISs reported in patients with ALD. Strikingly, most CISs in our experimental model and in patients with ALD cluster in megabase-wide chromosomal regions of high LV integration density. Conversely, cancer-triggering integrations at CISs found in tumor cells from γretroviral vector-based clinical trials and oncogene-tagging screenings in mice always target a single gene and are contained in narrow genomic intervals. These findings imply that LV CISs are produced by an integration bias toward specific genomic regions rather than by oncogenic selection.
Beschreibung:Gesehen am 23.03.2022
Beschreibung:Online Resource
ISSN:1528-0020
DOI:10.1182/blood-2010-09-306761

Ähnliche Einträge