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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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Blood, 15 March 2003, Vol. 101, No. 6, pp. 2167-2174
GENE THERAPY
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
François-Loïc Cosset
From the Laboratoire de Vectorologie
Rétrovirale et Thérapie Génique, Ecole Normale
Supérieure de Lyon, Lyon, France; Institut de
Génétique Moléculaire de Montpellier, Montpellier,
France; and Department of Genetics and Microbiology,
Faculty of Medicine, University of Geneva, Geneva,
Switzerland.
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 occur in these cells only 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 that 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 interleukin-7
(IL-7)-displaying HIV-1-derived vectors. Like 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, preactivation 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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