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Prepublished online as a Blood First Edition Paper on November 21, 2002; DOI 10.1182/blood-2002-07-2224.

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2002-07-2224v1
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Submitted July 24, 2002
Accepted October 22, 2002

IL-7 surface-engineered lentiviral vectors promote survival and efficient gene transfer in resting primary T lymphocytes

Els Verhoeyen, Valerie Dardalhon, Odile Ducrey-Rundquist, Didier Trono, Naomi Taylor, and Francois-Loic Cosset*

U412, ENS of Lyon, Lyon, France
UMR5535, IGMM, Montpellier, France
University of Geneva, Faculty of Medicine, Geneva, Switzerland

* Corresponding author; email: flcosset{at}ens-lyon.fr.

Important gene therapy target cells such as resting human T cells are refractory to transduction with lentiviral vectors. Completion of reverse transcription, nuclear import, and subsequent integration of the lentiviral genome only occur in these cells if they have been activated. In T cell based gene therapy trials performed to date, cells have been activated via their cognate antigen receptor. To couple activation with gene transfer, we previously generated lentiviral vectors displaying an anti-CD3 scFv fragment which allowed up to 48% transduction of freshly isolated T cells. However, transduction of highly purified resting T cells with these anti-CD3-displaying lentiviral vectors was inefficient and shifted the T cells from the naive to the memory phenotype. Here, we describe IL-7-displaying HIV-1-derived vectors. Like with recombinant IL-7, these modified particles could promote the survival of primary T cells placed in culture without inducing a naive to memory phenotypic switch. Furthermore, a single exposure to the IL-7-displaying vectors resulted in efficient gene transfer in both resting memory adult T cells and naive cord blood T cells. With adult naive T cells, pre-activation with recombinant IL-7 was necessary for efficient gene transfer. Altogether, these results suggest that IL-7-displaying vectors could constitute interesting tools for T-cell-targeted gene therapy.


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