Vectorisation d'oligonucleotides par la vitamine B2

Abstract : Antisense oligonucleotides and analogs, such as Peptide Nucleic Acids (PNA), are valuable tools to inhibit or modulate gene expression in a sequence-specific manner. Their successful application for therapeutic purposes is however hampered by poor cellular uptake or incorrect intracellular localization, and requires the development of efficient delivery strategies.Riboflavin, or vitamin B2, is an essential vitamin that could potentially be used as a targeting delivery ligand. We demonstrate in this PhD work the ability of two Riboflavin derivatives, Flavin and Lumichrome, to promote endocytosis-mediated internalization of PNA conjugates in several cell lines. Furthermore, a phenomenon of Photochemical Internalization produced by Rhodamine has been characterized using Flavin or Lumichrome - PNA - Rhodamine conjugatesand is responsible for an efficient release of these conjugates from endosomes. This PhD work has thus led to the characterization of a trifunctional conjugate for the internalization and cytoplasmic delivery of bioactive molecules.
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Fanny Marlin. Vectorisation d'oligonucleotides par la vitamine B2. Biologie moléculaire. Université Paris Sud - Paris XI, 2011. Français. ⟨NNT : 2011PA11T074⟩. ⟨tel-00743437⟩

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