Tesi sul tema "Vecteur cationique"
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Remy, Jean-Serge. "Synthese et utilisation in vitro de nouveaux vecteurs de transfert de genes". Strasbourg 1, 1994. http://www.theses.fr/1994STR15039.
Testo completoGrosse, Stéphanie. "Trafic intracellulaire de complexes plasmide/ polymères cationiques glycosylés dans des cellules épithéliales des voies aériennes humaines : application à la thérapie génique de la mucoviscidose". Paris 7, 2004. http://www.theses.fr/2004PA077087.
Testo completoGarcia, Chaumont Christine. "Etude in vitro de la vectorisation d'acides nucleiques par ama, un derive cationique de l'amphotericine b. (doctorat : pharmacotechnie et biopharmacie)". Paris 11, 1999. http://www.theses.fr/1999PA114840.
Testo completoColin, Morvane. "Transfert de gene par un vecteur non viral compose d'une sequence de ciblage des integrines et d'un liposome cationique : efficacite et devenir intracellulaire". Paris 6, 2000. http://www.theses.fr/2000PA066114.
Testo completoNouveau, Thibaut. "Nébulisation de nouveaux polyplexes pour le transfert de gènes". Electronic Thesis or Diss., Sorbonne université, 2023. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2023SORUS734.pdf.
Testo completoGene therapy is a form of therapy used to treat hereditary or acquired genetic diseases such as cancer or cystic fibrosis. Introducing a polynucleotide into diseased cells, either via the systmeic route or the local route (oral or nasal inhalation), corrects the defects causing the genetic mutations. However, DNA can only be internalized using a vector that protects it and enables it to reach the cell nucleus, where it will be transcribed. Various vectors (viral or synthetic) have been developed, such as PEI-based cationic polymer vectors. However, although effective, these PEI-based vectors are immunogenic at high doses. Functionalizations to reduce this toxicity, such as PEGylation, have been developed, making it possible to reinforce vectors by adding stealthiness to the final polyplexes. However, these strategies have their limitations, necessitating the synthesis of new types of polymer. POxylation represents a good alternative to PEG usage to form new polyplexes by adding a block formed from one or more poly(2-alkyl-2-oxazoline)s. The copolymers are synthesized by selective hydrolysis of a PEtOx-b-PnPrOx-b-PMeOx triblock copolymer using the thermosensitive properties of the hydrophobic blocks and a kosmotropic salt to form core-shell systems enabling hydrolysis of the PMeOx block to PEI. Then, the systems were formulated using a standard formulation and a "micro-extrusion" method. The polyplexes obtained were used in vitro experiments, by deposition or by a nebulization method, ideal for the treatment of pulmonary diseases. Very good transfection results were obtained, depending on various parameters (Mn, PEI, polymer architecture, +/- charge ratio)
Vaysse, Laurence. "Développement de vecteurs non viraux pour le transfert de gène dans l'épithélium respiratoire". Bordeaux 2, 2000. http://www.theses.fr/2000BOR28795.
Testo completoMasson, Christophe. "Transfert de gênes cible vers les tumeurs : conception, synthèse et propriétés de nouveaux vecteurs chimiques de l'ADN pour le ciblage des cellules cancéreuses". Paris 6, 2001. http://www.theses.fr/2001PA066166.
Testo completoMessai, Isabelle. "Élaboration de particules cationiques biodégradables comme vecteurs d'acides nucléiques". Lyon 1, 2004. http://www.theses.fr/2004LYO10162.
Testo completoDurand-Dal-Maso, Angélique. "Synthèse et évaluation de vecteurs cationiques pour le transport des gènes thérapeutiques". Toulouse 3, 2006. http://www.theses.fr/2006TOU30079.
Testo completoDevelopment of gene therapy is essentially based on gene transfer systems development. Considering the problems associated with viruses as delivery systems, synthetic vectors were proved to be promising alternative to viral-based systems. Our research project lies within the scope of a program developed within company CAYLA aiming at developing new synthetic vectors for gene transfer. In this work, we designed three synthetic cationic lipid families, phosphonoammonium, phosphonopyridium and phonosphono or amidopolyamine. Thus we synthesized compounds with phytanyl lipidic chains, that are until now little used, as gene transfer vectors. Moreover, a method for the synthesis of long dissymmetric chains of phosphite and phosphonate was developed. Finally, the in vitro transfection activity of these compounds was assessed on different cell lines. Promising results were obtained since some cationic lipids exhibited transfection properties comparable or even better than those commercially available and that are commonly used as references
Tranchant, Isabelle. "Conception et synthèse de vecteurs non cationiques pour le transfert de gènes". Paris 6, 2002. http://www.theses.fr/2002PA066356.
Testo completoLoizeau, Damien. "Étude des propriétés physicochimiques de phospholipides cationiques utilisés comme vecteurs de gènes". Brest, 2010. http://www.theses.fr/2010BRES2065.
Testo completoThe aim of the report is to study the formation and the physicochemical properties of liposomes and lipoplexes, in particular by fluorescence measurements, in order to determine the key factors for biological activity. First, we have optimized the formulation of the various compounds. We also showed that the number of charge and the length of the acyl chain strongly affect the formation of liposomes. Fluorescence measurements have shown correlation between structure and physicochemicals properties of liposomes. The presence of at least one insaturation allows to fluidify strongly the bilayer, furthermore the length of the acyl chain affects fusogenicity of liposomes. The last part of this work showed that there are different types of lipoplexes according to the CR. These influence strongly the proporties of the lipoplexes: low RC have slow kinetic of complexation and their transfection efficiency in vitro is sharply lower. Results in vivo confirmed the efficiency of some lipids but in a different order than in vitro, so it is necessary to study other parameters
Meunier, Durmort Claire. "Transfert de gènes dans des cellules différenciées par l'association d'adénovirus et de vecteurs cationiques". Paris 11, 1997. http://www.theses.fr/1997PA114814.
Testo completoPlet, Laëtitia. "Synthèse de nouveaux vecteurs cationiques à architecture en étoile pour le transfert de gènes". Electronic Thesis or Diss., Sorbonne université, 2019. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2019SORUS297.pdf.
Testo completoSome 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
Leblond-Chain, Jeanne. "Conception, synthèse et évaluation de systèmes de vectorisation non cationiques de l' ADN". Paris 6, 2005. https://pastel.archives-ouvertes.fr/pastel-00001738.
Testo completoLleres, David. "Nouvelles stratégies de vectorisation non virale impliquant des détergents cationiques : Caractérisation physicochimique et devenir intracellulaire des complexes vecteurs/ADN". Université Louis Pasteur (Strasbourg) (1971-2008), 2003. http://www.theses.fr/2003STR13184.
Testo completoThe success of gene therapy depends on the development of vectors able to efficiency deliver therapeutic gene into target cells. For in vivo applications, the size and the stability of vector/DNA complexes are key determinants for an efficient blood diffusion and intracellular trafficking. Within this framework, new synthetic vectors combining properties of cationic detergents and lipids were synthesized in the laboratory of J. P Behr. In spite of their favourable monomolecular DNA condensing properties, the transfection efficiency of these vectors was limited. In this context, in order to study the structure-activity relationship of these vectors, we have characterized the physicochemical properties of DNA complexed with dimerizable cationic detergents. By fluorescence spectroscopy, we have investigated their ability to condense DNA, the molecular order of the hydrophobic domains, and the stability of these complexes. Indeed, a minimal hydrocarbon tail length is required to stabilize the complexes. Moreover, a tight relationship between the stability of these complexes and their transfection efficiency was established. Based on these results, we have prepared new ternary complexes combining cationic liposomes and cationic detergents to DNA. By this strategy, we have formed small and stable ternary complexes. In the presence of serum, their transfection efficiency was higher than lipoplexes. Confocal microscopy observations suggested that ternary complexes were only marginally destabilized by serum and efficiently internalized into cells by endocytosis. Structural studies by electron microscopy and fluorescence spectroscopy associated with the monitoring of intracellular trafficking revealed that the internal lamellar organization of the complexes was strongly correlated with their colloidal stability and their high transfection efficiency in the presence of serum
Rogier-Floch, Virginie. "Etude de nouveaux vecteurs de synthèse de type lipides cationiques pour la transfection de cellules eucaryotes : application aux cellules souches hématopoi͏̈étiques (doctorat : sciences de la vie et de la santé)". Brest, 1998. http://www.theses.fr/1998BRES3101.
Testo completoRoques, Caroline. "Développement et évaluation de vecteurs de synthèse pour l'administration d'acides nucléiques dans le tissu musculaire". Paris 11, 2008. http://www.theses.fr/2008PA114814.
Testo completoOur work consisted in developing non-viral vectors mediating efficient and sage transfection of plasmid DNA in the striated muscles. Our interest was put on polymers based formulations and especially cationic homopolymers as well as amphiphilic block copolymers displaying few or no charges. The carriers obtained through the association between DNA and each polymer was first characterized. Those vectors were then optimized and submitted to the in vivo evaluation of their toxicity and transfection efficiency. Contrarily to the cationic polymer which appeared to be toxic towards striated muscles, carriers based on amphiphilic copolymers mediated no lesions. Moreover, we demonstrated that those carriers triggered relatively efficient transfection in the skeletal muscles. We also showed that an increase in transfection efficiency is observed when modulating some formulation parameters. Finally, we demonstrated that those carriers could efficiently transfer DNA to dystrophic muscle tissue
Gable-Guillaume, Christine. "Développement de vecteurs non viraux, de type lipides cationiques, pour la transfection, in vivo, chez la souris swiss : application à la mucoviscidose (doctorat : sciences de la vie et de la sante)". Brest, 1999. http://www.theses.fr/1999BRES3102.
Testo completoDelépine, Pascal. "Étude des voies d'administration et du devenir in vivo de vecteurs synthétiques pour le transfert de gènes : application à la mucoviscidose". Brest, 2004. http://www.theses.fr/2004BRES3103.
Testo completoCystic Fibrosis, the most common lethal genetic disease in Caucasian populations, is characterized by its great genotypic and phenotypic variability. This disease mainly affects both digestive and pulmonary functions, and the progressive respiratory degradation ultimately leads to death. Although many therapeutic strategies have emerged for the past decade, efficient treatments to cure permanently this disease are not available yet. Preventing the genetic defect would be the ideal way to achieve this goal. Since the CFTR gene, responsible for the disease was identified in 1989, gene therapy has become the major hope for CF patients. Many gene vectors, such as adenoviral-derived vectors and synthetic reagents have been evaluated to deliver therapeutic genes to the airways and numerous clinical trials have been initiated to assess both their safety and efficacy. Professor Férec, in Brest, has decided to penetrate this field by testing and developing a new family of cationic lipids for gene transfer to the lungs. Biodistribution of these reagents as well as kinetics of expression of the reporter genes were studied in vivo in mice following different ways of administration by various techniques, including imaging-based systems. Although we and others have collected a broad range of data including parameters influencing transfection efficiency and tissue targeting, a long and hard work is still to be done before gene therapy strategies can be routinely used as a common treatment to cure the CF disease
Lindberg, Mattias. "Développement, formulation et biodistribution de vecteurs synthétiques pour le transfert de gènes dans le cadre de la thérapie génique de la mucoviscidose". Thesis, Brest, 2012. http://theses-scd.univ-brest.fr/2012/These-2012-SICMA-Biologie_sante-LINDBERG_Mattias-Version_integrale.pdf.
Testo completoThe use of nucleic acids is a promising therapeutic approach in nanomedicine, in particular with the aim of remedying a genetic defect. Gene therapy for cystic fibrosis, namely the transfer of a normal copy of the CFTR gene into the epithelial cells of the respiratory tract of patients, requires particularly effective vectoring tools suitable for use in human clinics. If recombinant viruses are very efficient, their immunogenicity and oncogenic potential are all major drawbacks that synthetic vectors, and in particular cationic lipids, do not have. The subject of my thesis concerned the development and optimization of cationic lipids for gene transfer to the respiratory epithelium.In this work, we were able to demonstrate that the use of phytanyl aliphatic chains, on the latest generation arsenolipids, allowed the formation of reverse hexagonal phases, a supramolecular organization known to destabilize endocytosis vesicles and thus to promote cytosolic delivery of nucleic acids. Compared to its analogues, this new compound was particularly effective and not very toxic in vitro but also in mice, where a higher and more sustained expression of the transgene was observed in pulmonary epithelial cells after intravenous (IV) administration.We also investigated the various physiological damages caused by systemic administration oflipoplexes. We also used a plasmid optimized to allow sustained expression of the transgene.Acute inflammatory responses as well as a hepatic cytolysis were systematically observed in the first days after administration of the complexes, regardless of the presence of CG immunostimulatory motifs on the plasmid, the duration of transgene expression, or even the nature of the lipid. These phenomena last only a few days, while transgene could be expressed for more than 40 days using the codon-optimized plasmid. Efficient re-administration of lipoplexes was possible, but required sufficient time between each injection, emphasizing the importance of using nucleic acid constructs that give strong and stable transgene expressions.Intratracheal administration of judiciously prepared complexes also showed transgene expression kinetics (bioluminescence) of more than 100 days after a single administration.These results mark real progress in the structural optimization of vectors developed by our group as well as in their formulation, and encourage us to further exploit their potential for the transfer of genes to the lung
Montier, Tristan. "Développement et étude d'une nouvelle génération de vecteurs de synthèse de type lipides cationiques : application dans le cadre d'une thérapie génique de la mucoviscidose". Brest, 2003. http://www.theses.fr/2003BRES3103.
Testo completoLoisel, Séverine. "Optimisation et limites du transfert de gènes par voie intraveineuse à l'aide de vecteurs non viraux de type lipides cationiques chez la souris Swiss : application à une thérapie génique de la mucoviscidose (doctorat : sciences de la vie et de la santé)". Brest, 2000. http://www.theses.fr/2000BRES3104.
Testo completoReynier, Philippe. "Etude et évaluation de nouveaux lipides cationiques à base de cholestérol en tant que vecteurs d'adn dans des cellules tumorales in vitro et in vivo". Paris 13, 2003. http://www.theses.fr/2003PA132034.
Testo completoBelmadi, Nawal. "Développement, formulation et biodistribution de vecteurs synthétiques pour le transfert de gènes dans le cadre de la thérapie génique de la mucoviscidose". Thesis, Brest, 2015. http://www.theses.fr/2015BRES0093/document.
Testo completoCystic fibrosis is a monogenic disease characterized by mutations occurring at the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) gene. The clonining in 1989 of the CFTR gene has enabled to consider treating this disease by gene therapy. This consists of transferring a normal version of the CFTR gene in the affected patients’ cells, using a vector. Due to the severity of pulmonary complications, it is obvious that the respiratory epithelium constitutes the target tissue for the gene transfer. The principle of gene therapy is indeed very attractive and a number of clinical trials have already been made. Gene therapy requires vectorization tools that are efficient and compatible with repeated clinical use.My thesis has focused on the development, biodistribution and optimization of synthetic vectors (cationic lipids) for gene transfer in the respiratory epithelium. During my work, we were able to develop useful fluorescent KLN47 lipophosphoramidates for in vivo biodistribution studies. Compared to non fluorescent KLN47, these new compounds exhibit the same physicochemical properties: a relatively small size and a positive zeta potential. On cell lines, we found that the new formulations were as effective as the KLN47, with little or no toxicity. Then, in animal models, the biodistribution profiles of pegylated and non-pegylated lipoplexes were compared after systemic injection. The biodistribution profiles of pegylated and non-pegylated lipoplexes were similar. However, the pegylation of the complex resulted in prolonged circulation in the bloodstream, whereas transgene expression (luciferase) was equivalent in both cases. In addition, luciferase activity was similar to that obtained with the non-fluorescent KLN47. We have demonstrated that the addition of fluorescent lipid probes in the liposomal solution KLN47, does not change its physicochemical and transfectant properties. The overall results show that we have promising tools for in vivo biodistribution studies. Other molecules have also been tested successfully
Le, Bihan Olivier. "Etude par microscopie électronique des mécanismes d'action de vecteurs synthétiques pour le transfert de gènes". Thesis, Bordeaux 1, 2009. http://www.theses.fr/2009BOR13972/document.
Testo completoThe vast majority of clinical trials of gene transfer in vivo use viral vectors. Although they are effective, they induce immunogenic, toxic or mutagenic risks. Due to their high modularity and low toxicity, synthetic vectors (non viral), represent a promising alternative despite their lack of effectiveness. The major objective of this work was to understand the mechanism of gene transfer using two prototypic synthetic vectors, in the context of a rational design of new vectors. We studied on cultured cells, the mechanism of action of two cationic lipids; BGTC (bis(guanidinium)-tren-cholesterol) and DOSP (DiOleylamine A-Succinyl-Paromomycine) formulated with plasmid DNA (lipoplexes) which are in vitro efficient vectors. We have been able to visualize by electron microscopy, their intracellular pathways, their structural alterations and their endosomal escape, the latter being a key step in the process of gene transfer. The unambiguous identification of lipoplexes throughout their intracellular trafficking has been made possible thanks to the labelling of DNA by core-shell silica nanoparticles with an electron dense maghemite core (Fe2O3). The labeling strategy has also been applied to study the mechanism of action of a nonionic block copolymer (P188 or Lutrol). Interestingly, these synthetic vectors have an in vivo transfection efficiency in mice lung and muscle tissue while they are totally inefficient in vitro. We have shown that Lutrol induces an increase of DNA internalization into cells and fails to trigger endosomal escape, which would explain the lack of in vitro efficacy. These findings suggest that the in vivo mechanism of action of Lutrol would involve other internalization pathways
Laurent, Véronique. "Stratégie de vectorisation d'acides nucléiques et de drogues anticancéreuses dans les cellules hépatiques en culture". Phd thesis, Université Rennes 1, 2010. http://tel.archives-ouvertes.fr/tel-00518984.
Testo completoLeblond, Jeanne. "Conception, synthese, et évaluation de systemes non cationiques de vectorisation de l'ADN". Phd thesis, 2005. http://pastel.archives-ouvertes.fr/pastel-00001738.
Testo completo