Дисертації з теми "Gene and Molecular Therapy"
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Chen, Ian Ying-Li. "Molecular imaging of cardiac gene therapy /." May be available electronically:, 2008. http://proquest.umi.com/login?COPT=REJTPTU1MTUmSU5UPTAmVkVSPTI=&clientId=12498.
Повний текст джерелаLau, Cara Jean. "Gene therapy for malignant gliomas." Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=18478.
Повний текст джерелаLes gliomes sont des tumeurs primaires de cerveau les plus communes retrouvées dans les adultes. La survie médiane des patients diagnostiqués avec la forme la plus maligne, le glioblastome multiforme (GBM), est de 9 à 12 mois et a peu changé au cours des années en dépit des avances en technologie médicale. La thérapie génique peut offrir de nouvelles solutions pour traiter cette maladie résistante. Durant nos travaux, nous avons examiné trois stratégies différentes de thérapie génique Dans notre première étude, nous avons examiné l'efficacité de la thérapie visée à corriger des anomalies communes retrouvées dans les gliomes, comprenant l'amplification/mutation de récepteurs de type tyrosine kinase (RTK) et la perte de PTEN, qui mènent en conséquence à une voie activée de PI3K/Akt. Sans PTEN, les facteurs de transcription FOXO sont inactivés, et la cellule devient résistante à l'arrêt du cycle cellulaire et à l'apoptose. En utilisant un vecteur adénoviral (AdV) exprimant une protéine activée du mutant FOXO1 (AdFOXO1;AAA.), nous avons reconstitué les signaux pour l'arrêt du cycle cellulaire et l'apoptose in vitro ainsi que in vivo. Deuxièmement, nous avons examiné la capacité thérapeutique d'un nouveau vecteur adénovirale qui a la capacité de se répliquer sans provoquer de lyse cellulaire et qui exprime en plus la protéine de fusion uracile phosphoribosyltransférase/cytosine déaminase (CU). La protéine CU peut convertir le promédicament non-toxique, le 5-fluorocytosine (5-FC) à la drogue chimiothérapeutique diffusible, le 5-fluorouracile (5-FU) qui a comme cible des cellules en division cellulaire. In vitro, les vecteurs à capacité de répliquation étaient meilleurs que ceux qui ne pouvaient pas se répliquer. In vivo, le vecteur en présence du 5-FC a prolongé la survie de deux modès animaux (avec et sans sytèmes immunitaires). Dans un dernier temps, nous avons étudié une méthode pour exprimer l'IF
Katabi, Maha M. "Transcriptional targeting of suicide genes in cancer gene therapy." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape7/PQDD_0021/NQ55345.pdf.
Повний текст джерелаWallace, Lindsay M. "Gene Therapy for Facioscapulohumeral Muscular Dystrophy." The Ohio State University, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=osu1338315498.
Повний текст джерелаRohatgi, Priyanka. "Engineering Protein Molecular Switches To Regulate Gene Expression with Small Molecules." Diss., Georgia Institute of Technology, 2006. http://hdl.handle.net/1853/19852.
Повний текст джерелаYoshida, Jun. "Molecular Neurosurgery Using Gene Therapy to Treat Malignant Glinoma." 名古屋大学医学部, 1996. http://hdl.handle.net/2237/6179.
Повний текст джерелаThraser, Adrian James. "Molecular studies towards gene therapy for chronic granulomatous disease." Thesis, University College London (University of London), 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.307515.
Повний текст джерелаTiwari, Swati. "Gene Therapy Approaches for Hemophagocytic Lymphohistiocytosis." University of Cincinnati / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1447690858.
Повний текст джерелаMckiver, Bryan D. "SND1-Targeted Gene Therapy for Hepatocellular Carcinoma." VCU Scholars Compass, 2018. https://scholarscompass.vcu.edu/etd/5676.
Повний текст джерелаPerri, Sabrina R. "Exploiting the use of plasminogen kringle domains for cancer gene therapy." Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=103176.
Повний текст джерелаIn our first study, we assessed the angiostatic properties of the K5 peptide domain in an orthotopic brain cancer model. We demonstrated that the disulfide bridging conformation of K5, necessary to maintain its functionality, is conserved upon secretion by gene-modified mammalian cells. Kringle 5 retrovirally gene-engineered human U87 glioma cells produced functional soluble K5 protein capable of suppressing growth factor-induced endothelial cell migration in vitro and inhibiting glioma-induced angiogenesis in vivo. Interestingly, secreted K5 protein blocked the recruitment of tumor-associated CD45+Mac3 +Grl- macrophages in vivo and inhibited the migration of CD206+ human monocyte-derived macrophages in vitro. Moreover, in a clinically relevant orthotopic glioma model, soluble K5 induced long-term survival in a majority of test animals. Thus, these findings validate the use of a gene therapy approach to deliver Plg K5 protein and suggest that K5 acts as a novel 2-pronged anti-tumor agent, mediating its inhibitory effect via its action on host-derived endothelial cells and tumor-associated macrophages.
To determine if K5 mediated its anti-tumor effect by modulating other immune effector cells, we tested the use of soluble K5 in a murine DA/3 mammary adenocarcinoma model. Soluble K5 produced by retrovirally gene-modified DA/3 cells led to long-term survival (over 1 year) of immunocompetent BALB/c mice however, we failed to observe tumor rejection in immunodeficient NOD-SCID and BALB/c nude mice. Further analysis revealed that K5 enhances the recruitment of tumor-infiltrating CD3+ lymphoid cells, in particular the natural killer T (NKT)-lymphocyte phenotype. Consistent with our previous findings, we demonstrated that K5 led to a significant decrease in tumor-associated microvessel length and density. Interestingly, K5 tumors were characterized by a robust neutrophilic infiltrate. This may be explained by the ability of K5 to act as a strong chemotactic agent for human neutrophils in vitro as well as its ability to promote CD64+ activation within the CD11b+ neutrophil phenotype. These findings confirm that K5 acts as a potent angiostatic agent and possesses a novel pro-inflammatory role via its ability to recruit tumor-associated neutrophils and NKT-lymphocytes, leading to a strong anti-tumor response.
Tumor-associated macrophages (TAM) are key immune effector cells implicated in promoting tumor progression and metastasis. It would thus be desirable to explore strategies to reduce TAM infiltration within the tumor microenvironment. In our first study, we demonstrated that soluble K5 protein blocks macrophage recruitment. In addition, the recent observation that angiostatin reduces macrophage infiltration in an atherosclerosis model prompted our laboratory to further explore the use of angiostatin as an anti-macrophage agent. We demonstrated that angiostatin suppresses the in vitro migration of both murine peritoneal macrophages and human monocyte-derived CD206 + macrophages. Furthermore, we showed that angiostatin led to a decrease in the gelatinolytic activity of macrophage-produced matrix metalloproteinase-9, which may explain, in part, the observed angiostatin-mediated inhibition of migration. Additionally, we detected the presence of the beta-subunit of ATP synthase on the cell-surface of macrophages. ATP synthase was previously found to be a receptor for angiostatin on the cell-surface endothelial cells. We propose that the presence of ATP synthase on the surface of macrophages may promote interaction with angiostatin and prevent migration, similar to what has been reported with endothelial cells. Our findings suggest that angiostatin holds promise as an inhibitory agent against macrophages.
Taylor, Jennifer. "Engineering and improving a molecular switch system for gene therapy applications." Diss., Georgia Institute of Technology, 2011. http://hdl.handle.net/1853/39501.
Повний текст джерелаYogalingam, Gouri. "Molecular characterisation of feline MPS VI and evaluation of gene therapy /." Title page, contents and abstract only, 1998. http://web4.library.adelaide.edu.au/theses/09PH/09phy54.pdf.
Повний текст джерелаClarke, Don Lucas. "Development of a Stem Cell Gene Therapy for Sanfilippo Syndrome Type B." Thesis, California State University, Los Angeles, 2017. http://pqdtopen.proquest.com/#viewpdf?dispub=10278830.
Повний текст джерелаSanfilippo syndrome type B (Mucopolysaccharidosis type IIIB; MPS IIIB) is a lysosomal storage disorder affecting primarily the brain and is characterized by profound intellectual disability, dementia, and a lifespan of about twenty years. The cause is a mutation in the gene encoding α– N-acetylglucosaminidase (NAGLU), a lysosomal enzyme, leading to the deficiency of NAGLU and accumulation of heparan sulfate. I am investigating a stem cell gene therapy approach in a Naglu-/- mouse model. I think that iNSCs overexpressing NAGLU can engraft and reduce neural pathology in the mouse model. Here I report that NAGLU overexpressed in neural stem cells derived from induced pluripotent stem cells (iNSCs) is capable of being taken up by deficient cells. I used flow cytometry and Lysotracker to demonstrate that NAGLU can reduce deficient cells’ lysosomal volume in vitro, suggesting that NAGLU treatment has a biological effect. iNSCs overexpressing NAGLU were injected into the brains of 1 day old Naglu-/- mice. iNSCs were detected 10 weeks after injection. Brain sections possessed NAGLU activity greater than or equal to heterozygous controls, activity was detected distal to injection sites, and transplanted animals showed reduction in LAMP1, GFAP, and CD68. The results suggest that engineered iNSCs could be used to deliver enzyme and treat MPS IIIB.
Gwyther, Jacqueline Mary. "Molecular analysis and gene therapy of X-linked severe combined immunodeficiency disease." Thesis, University College London (University of London), 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.312004.
Повний текст джерелаTabebordbar, Mohammadsharif. "Improving Stem Cell-Based Therapy and Developing a Novel Gene Therapy Approach for Treating Duchenne Muscular Dystrophy (DMD)." Thesis, Harvard University, 2016. http://nrs.harvard.edu/urn-3:HUL.InstRepos:26718751.
Повний текст джерелаBiology, Molecular and Cellular
Larochelle, Nancy. "Gene therapy for muscular dystrophy : evaluation of a muscle-specific promoter for adenovirus-mediated gene transfer." Thesis, McGill University, 1998. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=20231.
Повний текст джерелаDomingo, i. Espín Joan. "Development and characterization of artificial viruses for gene therapy." Doctoral thesis, Universitat Autònoma de Barcelona, 2013. http://hdl.handle.net/10803/123204.
Повний текст джерелаThe biological risks associated to viral gene therapy limit the full development of viral vectors and pose major concerns to their incorporation into clinical trials. Non-viral gene therapy represents a safe alternative to natural viruses for cell targeted gene delivery, although the low gene expression levels achieved by non-viral vectors are a main obstacle for their therapeutic application. Different types of non-viral vectors have been developed up to date, including those based in liposomes, dendrimers or proteins. Recently, the ‘Artificial virus’ concept has been proposed to describe nanocomplexes for gene delivery that mimic the viral functions relevant to gene uptake and intracellular trafficking. Among them, those based on proteins and constructed through modular principles allow the incorporation, in a single polypeptide, of different proteins or protein domains with virus-like functions, namely DNA binding and condensation, receptor binding, internalization, endosomal escape, nuclear targeting and uncoating. We have developed a series of protein-only modular vehicles composed by different functional domains that are able to enter cells through specific receptor binding and promotes important levels of transgene expression. In this thesis this approach is discussed with two review articles and demonstrated with three original papers.
Guo, Hong. "Molecular therapy for peritoneal fibrosis targeting the TGF-b/Smad signaling pathway /." Click to view the E-thesis via HKUTO, 2007. http://sunzi.lib.hku.hk/HKUTO/record/B39557509.
Повний текст джерелаGuo, Hong, and 郭紅. "Molecular therapy for peritoneal fibrosis: targeting the TGF-{221}/Smad signaling pathway." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B39557509.
Повний текст джерелаBrennecke, Johannes. "Molecular diagnostics of the bacterial response to antibiotic therapy." Thesis, University of Edinburgh, 2017. http://hdl.handle.net/1842/28843.
Повний текст джерелаWang, Xiaoxia. "Molecular studies on the action of APOBEC3G against HIV-1 and development of an APOBEC-based anti-HIV approach." American Society for Microbiology, 2011. http://hdl.handle.net/1993/23226.
Повний текст джерелаHeller, Kristin Noreen. "Alternative to Gene Replacement for Duchenne Muscular Dystrophy using Human Alpha7 Integrin (ITGA7)." The Ohio State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=osu1388401639.
Повний текст джерелаZadro-Lamoureux, Laura. "XIAP (X-linked Inhibitor of Apoptosis) gene therapy protects photoreceptors in an animal model of retinal detachment-induced apoptosis." Thesis, University of Ottawa (Canada), 2009. http://hdl.handle.net/10393/28142.
Повний текст джерелаXu, Dan. "Cellular Immunity in Recombinant Adeno-Associated Virus Vector Mediated Gene Therapy." The Ohio State University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=osu1313504203.
Повний текст джерелаGade, Terence Peter Ferrante. "Integrated imaging of drug delivery : a molecular imaging approach to the optimization of cancer therapy /." Access full-text from WCMC:, 2007. http://proquest.umi.com/pqdweb?did=1432803381&sid=12&Fmt=2&clientId=8424&RQT=309&VName=PQD.
Повний текст джерелаConnolly, Richard J. "Plasma Mediated Molecular Delivery." Scholar Commons, 2010. http://scholarcommons.usf.edu/etd/3450.
Повний текст джерелаIreton, Gregory C. "Structural studies of yeast and bacterial cytosine deaminase : evolution and implications for anticancer gene therapy /." Thesis, Connect to this title online; UW restricted, 2003. http://hdl.handle.net/1773/5077.
Повний текст джерелаKim, Soo Hyun. "Gene therapy demonstrates that muscle is not a primary target for non-cell autonomous toxicity in familial ALS." Columbus, Ohio : Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1164829314.
Повний текст джерелаLandry, Sebastien. "Gamma-glutamyl carboxylase gene expression in cultured marrow stromal cells : significance for cell therapy of hemophilia B." Thesis, McGill University, 2003. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=80310.
Повний текст джерелаZhang, Xin. "Evaluation of hydrophobically modified low molecular weight chitosans as novel delivery vectors for non-viral gene therapy." Université Louis Pasteur (Strasbourg) (1971-2008), 2008. http://www.theses.fr/2008STR13003.
Повний текст джерелаThe success of gene therapy depends on the development of vectors able to deliver therapeutic genes into the cells. Among the non-viral vectors, chitosans are interesting since they are biocompatible and low toxic. We developed hydrophobically modified low molecular weight chitosans (HM-LMW-chs) that exhibit surfactant-like properties. HM(3%)-LMW-ch forms with DNA small positively charged particles that are resistant to DNases and nucleases and marginally interact with serum components. Moreover, these particles are efficiently internalized in cells and low toxic. After systemic administration, DNA complexes with HM(3%)-LMW-ch efficiently deliver genes in mice kidneys. Moreover, we developed a new two-photon absorbing (TPA) chromophore for two-photon imaging and conjugated it with PEI. The chromophore appears as an adequate tool to label the numerous polyamines used in non-viral gene delivery and characterize their complexes with DNA in two-photon applications
Packer, Davin R. "Leveraging the Extracellular Matrix to Create Novel Gene Therapies for the Congenital Muscular Dystrophies." The Ohio State University, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=osu1618248650165864.
Повний текст джерелаEriksson, Emma. "Preclinical evaluation of immunostimulatory gene therapy for pancreatic cancer." Doctoral thesis, Uppsala universitet, Institutionen för immunologi, genetik och patologi, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-330189.
Повний текст джерелаHallen, Michael Ryan. "Commercialization of a Novel Wound Therapy and Scar Prevention Product." Case Western Reserve University School of Graduate Studies / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=case1378942204.
Повний текст джерелаWreesmann, Volkert Boudewijn Singh Bhuvanesh. "Molecular-cytogenetic characterization of head and neck chancer identification of novel prognostic factors and gene targets for therapy /." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2004. http://dare.uva.nl/document/74975.
Повний текст джерелаPEREIRA, LARISSA M. "Clonagem, expressao, purificacao e caracterizacao estrutural da proteina ribossomal L10 humana recombinante." reponame:Repositório Institucional do IPEN, 2009. http://repositorio.ipen.br:8080/xmlui/handle/123456789/9478.
Повний текст джерелаMade available in DSpace on 2014-10-09T13:57:22Z (GMT). No. of bitstreams: 0
Dissertacao (Mestrado)
IPEN/D
Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP
Herron, John Paul. "Immunoaffinity isolation of Btk´s signalosome, a proteomic approach to identifying interacting proteins." Thesis, Södertörn University College, School of Life Sciences, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:sh:diva-1114.
Повний текст джерелаThe Signalosome is a term used to define a putative signalling complex, which assembles near the plasma membrane in response to external signals received at cell surface receptors and then migrates towards downstream effectors. It is proposed to regulate the level of intracellular Ca2+ and subsequent downstream signalling events. To date it has been defined to consist of BTK, BLNK, BCAP, VAV, PLCγ2 and PI3K1-4 in B-Cells.
This work entailed initiating a new proteomic approach to investigate the nature and extent of Bruton’s tyrosine kinase, Btk, involvement in the signalosome – inherently, the aim was to study multiple interactions of Btk with other molecules. By transfecting host cells with a Btk gene-transfer plasmid, virus particles were produced that were used to up-regulate and analyse the expression of Btk in three haematopoietic cell lines: B-cells, Pre-B-cells and a myeloid cancer cell. The construction of a new gene-transfer vector was successfully carried out by plasmid sub-cloning and it was subsequently found to effectively transfect the host cells and produce virus particles. The recombinant virus particles were employed with success in transducing three haematopoietic cell lines and with immunopurification and subsequent gel separation protein signalosome complexes were obtained ready for analysis by mass spectrometrical fingerprinting (to be carried out as a joint effort in Mount Sinai Hospital in Toronto, Canada).
Unzueta, Elorza Ugutz. "De novo design of self-assembling protein nanoparticles towards the gene therapy of colorectal cancer." Doctoral thesis, Universitat Autònoma de Barcelona, 2013. http://hdl.handle.net/10803/125920.
Повний текст джерелаCancer is ranked as the second leading cause of death worldwide. Consequently there is a huge necessity of finding more effective cancer therapies. Currently available cancer therapies, far from being effective, present high systemic toxicity and low patient survival rates being the main mortality cause the appearance of metastatic foci, especially in colon cancer. Thus, improving cell specificity and avoiding metastases generation are the mayor challenges for future cancer therapies. In this context, gene therapy appears as very promising alternative therapy since cell targeted personalized therapies can be performed with low systemic toxicity. Since biosafety is the current mayor concern in this type of therapies, multifunctional proteins appear as the most promising gene therapy vectors because of their high biocompatibility and biosafety, low toxicity and really complete tuneability. Moreover, the necessity of effectively controlling nanoparticles size for their efficient biodistribution and delivery has been widely described in the literature. In the present work has been explored the possibility of effectively modulating the self-assembling of multifunctional protein building blocks into predefined size distribution nanoparticles in order to get the full potential of those protein-only nanoparticles for their application in therapeutic drugs and nucleic acids delivery approaches. In this regard, we have described cationic architectonic tag pairs ( one of them being a poly-histidine) that when incorporating to proteins, they induce the self-assembling of protein monomers into nanoparticles with predefined structural properties. It has also been studied the interaction and intracellular trafficking of these kind of protein nanoparticles in cultured cells proving not to be toxic for mammalian cells. Moreover, the structural stability of generated nanoparticles upon intravenous administration in mice has been also studied proving in vitro generated intermolecular interactions during protein assembling process strong enough to ensure nanoparticles structural stability in vivo. It has been shown that CXCR4 chemoquine receptor is a key element in metastasis formation during cancer evolution in different types of tumors, including colorectal cancer, for which metastatic intracellular targeting vehicles are currently missing. In this context, the possibility of effectively functionalizing protein nanoparticles with CXCR4 specific ligands has been deeply explored in this study. Among tested peptide ligands, T22 peptide has shown to be an unusually powerful tag for selective intracellular targeting in CXCR4+ cells having T22-empowered protein nanoparticles of optimal size selectively biodistribute in CXCR4+ cells in vivo. Finally, the suitability of functionalized self-assembling protein nanoparticles for their use as artificial viruses has been also extensively explored. Protein nanoparticles that contain nucleic acid binding domains have shown an appealing capacity to generate virus-like structures when combined with external DNA, completely shielding cargo DNA in the inner part of the structure and protecting it from external nucleases hydrolysis. However, the necessity of an additional DNase/RNase hydrolysis treatment during the nanoparticles purification process has been described since nanoparticles with nucleic acid binding domains have been shown to bind nucleic acids from the bacterial host used for their recombinant expression, resulting strongly detrimental for their functionality as artificial viruses. All together, the high biocompatibility expected for proteins, their regulatable architectonic properties and their efficient targeting possibility, make self-assembling protein-only nanoparticles a very promising material for the therapeutic delivery of drugs and nucleic acids in metastatic colorectal cancer cells and in general in mammalian cells.
Gopinath, Puja Gopinath. "A Review of Pricing and Reimbursement for Abeona Theraputics’ Gene Therapy Products to Treat Sanfilippo Syndrome." Case Western Reserve University School of Graduate Studies / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=case1497024647261096.
Повний текст джерелаOliveira, Franciele de Paula Pansani [UNESP]. "Síntese, caracterização e estudo físico-químico das nanopartículas formadas pela interação de amino derivados de quitosana com DNA." Universidade Estadual Paulista (UNESP), 2011. http://hdl.handle.net/11449/97737.
Повний текст джерелаO presente trabalho apresenta a síntese e caracterizaçao de derivados de quitosana obtidos pela reação com cloreto de 2-cloro dietilaminoetilamônio (DEAE Cl). Os derivados obtidos foram utilizados na síntese de nanopartículas para liberação controlada de genes. Inicialmente a quitosana comercial foi desacetilada e as sínteses foram realizadas em meio aquoso alcalino pela reação de substituição nucleofílica dos grupos amino da quitosana. A caracterização dos derivados foi realizada utilizando-se a espectroscopia de ressonância magnética nuclear de prótons (RMN-1 H), titulações potenciométricas e condutimétricas. Os derivados obtidos apresentaram proporções crescentes de DEAE (15%, 24%, 80% e 117%) e diferentes capacidades de tamponamento. A massa molecular viscosimétrica foi determinada por medidas de viscosidade e variou de 17 a 21 kDa. As titulações potenciométricas mostraram que a modificação de quitosana com o grupo DEAE permite aumentar a capacidade tamponante com respeito à quitosana e pode contribuir para aumentar a liberação de DNA e a eficiência do processo de transfecção gênica. O estudo dos derivados com DNA foi realizado utilizando-se as técnicas de fluorescência, eletroforese, espalhamento de luz dinâmico (tamanho das nanopartículas) e potencial zeta. O ensaio com brometo de etídio mostrou que a força de interação de DNA com os derivados depende tanto do grau de substituição por DEAE quanto da razão de cargas (N/P). Em altos valores de pH (7,4) todos os derivados interagem fortemente com DNA devido a presença dos grupos amino terciários e quaternários ligados a cadeia de quitosana. Os resultados de eletroforese mostram que a força de interação aumenta com o grau de substituição de DEAE e os resultados iniciais de espalhamento de luz mostram que nanopartículas estáveis podem ser obtidas em pH fisiólogico...
This work presents the synthesis and characterization of chitosan derivatives obtained by reaction of chitosan with diethylaminoethyl chloride - Cl DEAE. The obtained derivatives were employed in the synthesis of nanoparticles for controlled delivery of genes. Commercial chitosan was deacetylated and the reactions were carried out in aqueous solution at pH 8.0 by the nucleophilic subsitituion of the chitosan amino groups. The characterization was performed using 1H NMR spectroscopy, potentiometric and conductimetric titrations. The obtained derivatives contain increasing proportions of DEAE (15%, 24%, 80% and 117%) and different buffering capacities. Viscosity measurements were performed to determine the viscoimetric molecular weight (Mv), which varied from 17 to 21 kDa. The potentiometric titrations showed that DEAE groups increase the buffering capacity of chitosan and this may contribute to increase the DNA delivery from nanoparticles and the efficiency of gene transfection. The study of interaction between the derivatives and DNA was performed using fluorescence, gel electrophoresis, dynamic light scattering and zeta potential. The ethidium bromide (EtBr) assay showed that the strenght of interaction between the derivatives and DNA depends on both, the degree of substitution (DS) and N/P charge ratio. At physiological pH all derivatives interacted with DNA due to the presence of tertiary quaternary amino groups attached to the chitosan main chain. The gel electrophoresis results showed that the strength of interaction increases with DS and the initial results employing light scattering techniques show that stable nanoparticles can be obtained in phyisological pH, which is clearly an important property in comparison to deacetylated chitosan. Transfection studies carried out with these derivatives confirmed that the presence of DEAE groups improves the transfection efficiency... (Complete abstract click electronic access below)
BASÍLIO, João Paulo Santana. "Genetic engineering of human cell lines for the improvement of viral vector production for gene therapy." Master's thesis, Instituto de Higiene e Medicina Tropical, 2018. http://hdl.handle.net/10362/61545.
Повний текст джерелаGene therapy using viral vectors harnesses naturally occurring viral biological mechanisms to deliver therapeutic genes and control their expression in patient target cells. Several viral gene therapy products have already reached the market, with nearly half being based on recombinant viruses belonging to the Retroviridae family. These are a frequent option since they have large genetic payload capacity, high transduction efficiency, stable genome integration in transcriptionally active loci of dividing and non-dividing cells and sustained long-term expression of the delivered gene. Revenue predictions for viral gene therapy market in 2020 surpass 200 million US dollars, with no decline perspective until at least 2026. Yet, recombinant retroviral synthesis faces several challenges. High non-infective particle concentration – roughly 1 in every 1000 produced particles are infective – and low yields of current production platforms, both of which impose high production costs, present the hardest barriers to overcome in clinical to market transition. Previously, metabolic pathways recruited in recombinant retroviral production were identified. In this work, five target genes were overexpressed in a stable recombinant retrovirus producer cell line through lentiviral vector transduction with incremental target gene expression. The five considered genes – BCL2, GSR, HSPA5, PDIA and XBP1 – belong to pathways involved in anti-apoptosis, glutathione metabolism and endoplasmic reticulum protein synthesis. Resulting populations were characterized for cell growth, recombinant retrovirus productivity, viral components and metabolic gene expression. Increase in productivity was associated to overexpression of genes intervenient in endoplasmic reticulum protein synthesis. Increases of 140% were obtained with XBP1 gene – which is associated to unfolded protein response and thus, correct protein folding. More modest increases of 63% were attributed to PDIA2 gene – which is associated to disulfide bond catalysis. Lastly, increases of 73% can be observed with HSPA5 – which is associated to a wide range of protein synthesis processes within the endoplasmic reticulum. Improvements in productivity were not observed with anti-apoptotic nor glutathione associated genes, namely BCL2 and GSR. The results herein obtained demonstrate cell metabolic engineering as a valuable strategy to improve recombinant retroviral production. Three of the five targeted genes resulted in higher recombinant retroviral production supporting protein synthesis as powerful targets for debottlenecking recombinant retroviral production. This work contributes for the viral gene therapy field. The knowledge generated in this work is relevant to other viral vectors and for metabolic engineering of human derived cell lines.
Morin, Nicolas. "Expression of mutated HIV-1 Gag-Pol proteins and their effects on virus replication and infectiousness, implications for gene therapy." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape16/PQDD_0015/MQ37152.pdf.
Повний текст джерелаVillalobos, Alberú Xenia. "Polypurine Reverse Hoogsteen hairpins: stability, lack of immunogenicity and gene silencing in cancer therapy." Doctoral thesis, Universitat de Barcelona, 2015. http://hdl.handle.net/10803/360588.
Повний текст джерелаEste trabajo se centra en el estudio de la estabilidad y potencial inmunogénico de las moléculas llamadas PPRHs (Polypurine Reverse Hoogsteen hairpins), y en su uso como herramienta de silenciamiento génico. Los PPRHs son moléculas de DNA no modificadas. Están formadas por dos cadenas antiparalelas de polipurinas unidas por un bucle pentatimidínico, lo que permite la formación intramolecular de enlaces de Hoogsteen reversos entre ambas cadenas. Anteriormente se demostró que los PPRH son capaces de unirse a una secuencia de dsDNA mediante enlaces de Watson-Crick, formando un triplex que desplaza la cadena polipurínica de la diana. La prueba de principio para el uso de los PPRH como agente terapéuticos se llevó a cabo con un PPRH dirigido al gen de la survivina el cual fue validado tanto in vitro como in vivo. En esta tesis se ha profundizado en el conocimiento de los PPRHs. Se ha establecido que estas moléculas son estables en diferentes tipos de suero, así como intracelularmente. Además se determinó que los PPRHs, no inducen la activación de la respuesta inmune innata, ya que su transfección a una línea monocítica no incrementó los niveles de expresión de los factores de transcripción IRF3 y NF-κB, y tampoco de las citoquinas proinflamatorias IL-6, TNF-α, IFN-α, IFN-β, IL-1β, y IL-18. Además, los PPRHs no indujeron la activación del inflamasoma. También se diseñaron dos estructuras nuevas de PPRH: PPRH circulares y PPRHs basados en RNA, y se estudiaron diversos parámetros como su capacidad de unión a la diana y su citotoxicidad. Para ampliar la aplicabilidad de estas moléculas, se validó el uso de los PPRHs sobre diversos genes relevantes en cáncer: BCL2, MDM2, MYC, TOP1 y MTOR. Esta validación se realizó en diversas líneas tumorales (PC3, MIA PaCa-2, HCT116, SKBR3, MCF7 y MDA-MB-468) observando que los PPRHs fueron capaces de disminuir la supervivencia de las células y la expresión de los genes diana, y de aumentar la apoptosis. Finalmente, se realizó una aproximación para incrementar la especificidad de los PPRHs, la cual incluye el uso de un aptámero de DNA dirigido a la proteína de membrana HER2.
Lang, Annemarie [Verfasser]. "Reviewing Challenges in Osteoarthritis Gene Therapy and Introduction of a Molecular Therapeutic Approach in an Equine Model System / Annemarie Lang." Berlin : Freie Universität Berlin, 2016. http://d-nb.info/1099282764/34.
Повний текст джерелаKnoop, Kerstin. "Molecular imaging and radionuclide therapy in non-thyroidal tumors after mesenchymal stem cell- mediated sodium/iodide symporter (NIS) gene transfer." Diss., Ludwig-Maximilians-Universität München, 2014. http://nbn-resolving.de/urn:nbn:de:bvb:19-178550.
Повний текст джерелаChoudhury, Sourav Roy. "Developing an Adeno-Associated Viral Vector (AAV) Toolbox for CNS Gene Therapy: A Dissertation." eScholarship@UMMS, 2016. https://escholarship.umassmed.edu/gsbs_diss/809.
Повний текст джерелаChoudhury, Sourav Roy. "Developing an Adeno-Associated Viral Vector (AAV) Toolbox for CNS Gene Therapy: A Dissertation." eScholarship@UMMS, 2001. http://escholarship.umassmed.edu/gsbs_diss/809.
Повний текст джерелаAlamoudi, Aliaa. "Regulated antagonism of immune suppressive molecules in tumours." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:95599708-58e8-4a35-92b9-4e31523556f3.
Повний текст джерелаSingh, Preetinder Pal Clinical School Prince of Wales Hospital Faculty of Medicine UNSW. "A combination of molecular and traditional chemotherapy: prospects of synergies against cancer." Awarded by:University of New South Wales. Clinical School - Prince of Wales Hospital, 2009. http://handle.unsw.edu.au/1959.4/44564.
Повний текст джерелаSalazar, Marcela d'Alincourt. "Genomic Effects of Hormonal Adjuvant Therapies that Could Support the Emergence of Drug Resistance in Breast Cancer." University of Toledo Health Science Campus / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=mco1280929084.
Повний текст джерелаMarrero, Bernadette. "Evaluation of Immunogene Therapy Using a Plasmid Encoding IL-15 Delivered by Electroporation in a 3D Tumor Model and a Mouse Melanoma Model." Scholar Commons, 2010. http://scholarcommons.usf.edu/etd/3520.
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