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Synthèse de nouveaux vecteurs cationiques à architecture en étoile pour le transfert de gènes

Abstract : Some rare diseases of genetic origin can be treated by a therapy called "gene therapy" which consists in introducing a polynucleotide (DNA or RNA) into the cells to modulate their activity for therapeutic purposes. The use of a vector able to protect the polynucleotide and to transport it to the nucleus of the target cells is necessary. Polyethyleneimine (PEI) is currently the cationic polymer gold standard in this field. However, due to its high toxicity, many studies aiming to modify PEI are still underway to improve its properties. Among other things, it has been shown that compact architectures give better properties to polymers. In this context, star PEI were synthesized for the first time. To this end, star poly(2-oxazoline)s precursors were prepared and their architecture was confirmed by steric exclusion chromatography analyses and kinetic studies. PEI of variable molar mass (8, 16 and 25 K) and architecture (linear, 3 and 4 arms star) were then obtained by adapting the hydrolysis protocol used for linear polymers. The transfection of CFBE and HepG2 cells with polyplexes based on pDNA and these polymers was evaluated. The influence of molar mass and architecture was studied. Finally, the modification of these PEI with histidine moieties known to increase lPEI transfection efficiency was successfully achieved, however, the expected synergy between the chemical and architectural modifications was not observed for the in vitro transfection of HepG2 cells.
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Submitted on : Monday, December 6, 2021 - 1:02:17 AM
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  • HAL Id : tel-03466540, version 1


Laëtitia Plet. Synthèse de nouveaux vecteurs cationiques à architecture en étoile pour le transfert de gènes. Polymères. Sorbonne Université, 2019. Français. ⟨NNT : 2019SORUS297⟩. ⟨tel-03466540⟩



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