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Transfert du gène d'intérêt thérapeutique p53 par internalisation photochimique de complexes p53/polyethylenimine : applications pour le traitement des cancers épidermoïdes de la tête et du cou

Abstract : P53 abnormalities are found in more than 50% HNSCC and are associated with bad prognosis and resistance to conventional therapies. Gene therapy, which consists in the correction of gene default by the reintroduction of external wild-type gene, is an emerging therapeutic modality for the treatrnent of cancer. The nonviral vectors are limited by their low transfection efficiency. The present study was designed to study the influence of photochemical internalisation (PCI) on polyethylenimine (PEI)-mediated wild-type p53 gene transfer in HNSCC cells and xenografts bearing p53 mutations. The PCI is a light-directed gene transfer technology that has been reported to significantly enhance the transfection efficiency of several nonviral vectors. After the optimisation of the experirnental conditions for PCI and PEI, we showed that this combination led to a significant increase of the transgene expression level and duration either in vitro or in vivo. Indeed, in vitro, the combination of PCI and PEI for p53 gene transfer further restored the p53 rnRNA and protein expression with a subsequent induction of apoptosis and cell growth inhibition. In vivo, the use of PCI and PEI led to higher and long- lasting transgene expression that was correlated with subsequent tumor eradication by mean of p53-dependant apoptosis.
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Theses
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http://docnum.univ-lorraine.fr/prive/SCD_T_2005_0226_NDOYE.pdf
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https://hal.univ-lorraine.fr/tel-01746983
Contributor : Thèses Ul <>
Submitted on : Thursday, March 29, 2018 - 10:49:00 AM
Last modification on : Thursday, July 2, 2020 - 3:42:06 PM

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  • HAL Id : tel-01746983, version 1

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Alioune Ndoye. Transfert du gène d'intérêt thérapeutique p53 par internalisation photochimique de complexes p53/polyethylenimine : applications pour le traitement des cancers épidermoïdes de la tête et du cou. Biotechnologies. Université Henri Poincaré - Nancy 1, 2005. Français. ⟨NNT : 2005NAN11307⟩. ⟨tel-01746983⟩

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