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ZAP-70 restoration in mice by in vivo thymic electroporation

Saade, Murielle
Kissenpfennig, Adrien
Poulin, Lionel Franz
Leserman, Lee
Marche, Patrice N.
Jouvin-Marche, Evelyne
Berger, Francois
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Published in PloS one. 2008, vol. 3, no. 4, e2059
Abstract Viral and non-viral vectors have been developed for gene therapy, but their use is associated with unresolved problems of efficacy and safety. Efficient and safe methods of DNA delivery need to be found for medical application. Here we report a new monopolar system of non-viral electro-gene transfer into the thymus in vivo that consists of the local application of electrical pulses after the introduction of the DNA. We assessed the proof of concept of this approach by correcting ZAP-70 deficient severe combined immunodeficiency (SCID) in mice. The thymic electro-gene transfer of the pCMV-ZAP-70-IRES-EGFP vector in these mice resulted in rapid T cell differentiation in the thymus with mature lymphocytes detected by three weeks in secondary lymphoid organs. Moreover, this system resulted in the generation of long-term functional T lymphocytes. Peripheral reconstituted T cells displayed a diversified T cell receptor (TCR) repertoire, and were responsive to alloantigens in vivo. This process applied to the thymus could represent a simplified and effective alternative for gene therapy of T cell immunodeficiencies.
Keywords AnesthesiaAnimalsCell DifferentiationElectric ConductivityElectroporation/*methodsGreen Fluorescent Proteins/metabolismImmunophenotypingLymphoid Tissue/cytologyMiceReceptors, Antigen, T-Cell/metabolismSpleen/cytologyT-Lymphocytes/cytologyThymus Gland/*cytologyTime FactorsTransfectionZAP-70 Protein-Tyrosine Kinase/deficiency/*metabolism
PMID: 18446234
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IRLA, Magali et al. ZAP-70 restoration in mice by in vivo thymic electroporation. In: PloS one, 2008, vol. 3, n° 4, p. e2059. doi: 10.1371/journal.pone.0002059 https://archive-ouverte.unige.ch/unige:19020

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Deposited on : 2012-03-27

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