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 Blood, 8 October 2009, Vol. 114, No. 15, pp. 3173-3180.
Prepublished online as a Blood First Edition Paper on August 10, 2009; DOI 10.1182/blood-2009-05-220798.

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GENE THERAPY

Efficient and stable transduction of resting B lymphocytes and primary chronic lymphocyte leukemia cells using measles virus gp displaying lentiviral vectors

Cecilia Frecha1, Caroline Costa1, Camille Lévy1, Didier Nègre1, Stephen J. Russell2, Andrea Maisner3, Gilles Salles4, Kah-Whye Peng2, Francois-Loïc Cosset1,*, and Els Verhoeyen1,*

1 Inserm U758, Human Virology Department, Université de Lyon, Ecole Normale Supérieure de Lyon, Lyon, France; 2 Department of Molecular Medicine, Mayo Clinic, Rochester, MN; 3 Institut für Virologie, Philipps-Universität Marburg, Marburg, Germany; and 4 Hospices Civils de Lyon; Université Lyon 1, Unité Mixte de Recherche Centre National de la Recherche Scientifique 5239, Lyon, France

Up to now, no lentiviral vector (LV) tool existed to govern efficient and stable gene delivery into quiescent B lymphocytes, which hampers its application in gene therapy and immunotherapy areas. Here, we report that LVs incorporating measles virus (MV) glycoproteins, H and F, on their surface allowed transduction of 50% of quiescent B cells, which are not permissive to VSVG-LV transduction. This high transduction level correlated with B-cell SLAM expression and was not at cost of cell-cycle entry or B-cell activation. Moreover, the naive and memory phenotypes of transduced resting B cells were maintained. Importantly, H/F-LVs represent the first tool permitting stable transduction of leukemic cancer cells, B-cell chronic lymphocytic leukemia cells, blocked in G0/G1 early phase of the cell cycle. Thus, H/F-LV transduction overcomes the limitations of current LVs by making B cell–based gene therapy and immunotherapy applications feasible. These new LVs will facilitate antibody production and the study of gene functions in these healthy and cancer immune cells.


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