TY - JOUR
T1 - Stable transduction of quiescent T cells without induction of cycle progression by a novel lentiviral vector pseudotyped with measles virus glycoproteins
AU - Frecha, Cecilia
AU - Costa, Caroline
AU - Nègre, Didier
AU - Gauthier, Emmanuel
AU - Russell, Stephen J.
AU - Cosset, François Loïc
AU - Verhoeyen, Els
PY - 2008/12/15
Y1 - 2008/12/15
N2 - A major limitation of current lentiviral vectors (LVs) is their inability to govern efficient gene transfer into quiescent cells such as primary T cells, which hampers their application for gene therapy. Here we generated high-titer LVs incorporating Edmonston measles virus (MV) glycopro-teins H and F on their surface. They allowed efficient transduction through the MV receptors, SLAM and CD46, both present on blood T cells. Indeed, these H/F-displaying vectors outperformed by far VSV-G-LVs for the transduction of IL-7-prestimulated T cells. More importantly, a single exposure to these H/F-LVs allowed efficient gene transfer in quiescent T cells, which are not permissive for VSV-G-LVs that need cell-cycle entry into the G1b phase for efficient transduction. High-level transduction of resting memory (50%) and naive (11%) T cells with H/F-LVs, which seemed to occur mainly through SLAM, was not at cost of cell-cycle entry or of target T-cell activation. Finally, the naive or memory phenotypes of transduced resting T cells were maintained and no changes in cytokine profiles were detected, suggesting that T-cell populations were not skewed. Thus, H/F-LV transduction of resting T cells overcomes the limitation of current lenti-viral vectors and may improve the efficacy of T cell-based gene therapy.
AB - A major limitation of current lentiviral vectors (LVs) is their inability to govern efficient gene transfer into quiescent cells such as primary T cells, which hampers their application for gene therapy. Here we generated high-titer LVs incorporating Edmonston measles virus (MV) glycopro-teins H and F on their surface. They allowed efficient transduction through the MV receptors, SLAM and CD46, both present on blood T cells. Indeed, these H/F-displaying vectors outperformed by far VSV-G-LVs for the transduction of IL-7-prestimulated T cells. More importantly, a single exposure to these H/F-LVs allowed efficient gene transfer in quiescent T cells, which are not permissive for VSV-G-LVs that need cell-cycle entry into the G1b phase for efficient transduction. High-level transduction of resting memory (50%) and naive (11%) T cells with H/F-LVs, which seemed to occur mainly through SLAM, was not at cost of cell-cycle entry or of target T-cell activation. Finally, the naive or memory phenotypes of transduced resting T cells were maintained and no changes in cytokine profiles were detected, suggesting that T-cell populations were not skewed. Thus, H/F-LV transduction of resting T cells overcomes the limitation of current lenti-viral vectors and may improve the efficacy of T cell-based gene therapy.
UR - http://www.scopus.com/inward/record.url?scp=58149380748&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=58149380748&partnerID=8YFLogxK
U2 - 10.1182/blood-2008-05-155945
DO - 10.1182/blood-2008-05-155945
M3 - Article
C2 - 18812471
AN - SCOPUS:58149380748
SN - 0006-4971
VL - 112
SP - 4843
EP - 4852
JO - Blood
JF - Blood
IS - 13
ER -