Дисертації з теми "RNA therapeutic"
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Kavitha, Siva. "RNA-based therapeutic approaches for FTDP-17." Doctoral thesis, Università degli studi di Trento, 2015. https://hdl.handle.net/11572/367651.
Повний текст джерелаKavitha, Siva. "RNA-based therapeutic approaches for FTDP-17." Doctoral thesis, University of Trento, 2015. http://eprints-phd.biblio.unitn.it/1552/1/PhD_thesis_Siva_K_June_2015.pdf.
Повний текст джерелаWhite, Melanie Denise. "RNA interference as a therapeutic approach in prion disease." Thesis, University College London (University of London), 2008. http://discovery.ucl.ac.uk/1445182/.
Повний текст джерелаWu, Connie Ph D. Massachusetts Institute of Technology. "Engineering periodic short hairpin RNA delivery systems for enhanced therapeutic efficacy." Thesis, Massachusetts Institute of Technology, 2019. https://hdl.handle.net/1721.1/121821.
Повний текст джерелаCataloged from PDF version of thesis.
Includes bibliographical references.
RNA interference (RNAi) presents a highly promising approach for cancer therapeutics via specific silencing of disease-implicated genes, but its clinical translation remains severely limited by barriers in delivering short interfering RNA (siRNA). Numerous delivery vehicles have been developed to protect siRNA from degradation, promote target cell uptake, and facilitate endosomal escape into the cytoplasm, where RNAi occurs. However, in vivo instability, low silencing efficiency, undesired toxicity, and immunogenicity remain challenges for current siRNA delivery systems, particularly as the low valency and high rigidity of siRNA make it difficult to condense into stable nanoparticles. Here we engineer the siRNA cargo to make it more amenable to stable encapsulation by using a polymeric form of siRNA, or periodic short hairpin RNA (p-shRNA), as well as design a biodegradable polycationic carrier for efficient in vivo delivery of p-shRNA.
Consisting of tens of linked siRNA repeats, p-shRNA is synthesized by the repeated action of T7 RNA polymerase around a circular DNA template. We first leverage molecular engineering design an open-ended p-shRNA structure that is efficiently processed inside cells into siRNAs, greatly enhancing its silencing potency. Furthermore, the much higher valency and flexibility of p-shRNA compared to siRNA enable more stable complexation with delivery materials. To exploit these advantages of p-shRNA, we optimize biodegradable polycations with hydrophobic regions that promote stable condensation and efficient intracellular release. Our approach unveils key design rules governing p-shRNA delivery, and we develop stabilized p-shRNA complexes that show in vivo therapeutic efficacy in a syngeneic melanoma mouse model. Finally, we extend our p-shRNA platform to act as a dual therapeutic agent, harnessing innate immune activation together with gene silencing.
By modulating the surface of the p-shRNA complexes with an anionic polypeptide, we dramatically enhance innate immune recognition of p-shRNA by pattern recognition receptors while maintaining high silencing efficiency. These dually acting complexes can target ovarian tumors in vivo and prolong survival in a syngeneic ovarian cancer mouse model. Our findings establish a potent, multifunctional RNAi platform that can potentially move RNAi therapeutics closer to clinical translation by addressing the delivery and in vivo efficacy challenges faced by current siRNA systems.
National Science Foundation Graduate Research Fellowshipgrant #1122374
Koch Institute Ludwig Center for Molecular Oncology Graduate Fellowship
Congressionally Directed Medical Research Program Ovarian Cancer Research Program Teal Innovator Award from the Department of Defense (13-1-0151)
by Connie Wu.
Ph. D.
Ph.D. Massachusetts Institute of Technology, Department of Chemical Engineering
BALESTRA, Dario. "Modified U1snRNAs as innovative therapeutic strategy for inherited coagulation factor deficiencies." Doctoral thesis, Università degli studi di Ferrara, 2012. http://hdl.handle.net/11392/2388781.
Повний текст джерелаAl-Mazedi, Maryam. "A therapeutic approach to chronic myeloid leukaemia using short hairpin RNA molecules." Thesis, King's College London (University of London), 2012. https://kclpure.kcl.ac.uk/portal/en/theses/a-therapeutic-approach-to-chronic-myeloid-leukaemia-using-short-hairpin-rna-molecules(185139fb-ed9b-46d7-a5a8-04532c44640b).html.
Повний текст джерелаJubair, Luqman Khaleel. "Next-Generation Cancer Therapies: The Therapeutic Potential of RNA-Directed Gene-Editing." Thesis, Griffith University, 2018. http://hdl.handle.net/10072/382679.
Повний текст джерелаThesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Medical Science
Griffith Health
Full Text
Elmén, Joacim. "Nucleic acid based therapeutic approaches /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-047-8/.
Повний текст джерелаHong, Lingzi. "Act1-Mediated RNA Metabolism in IL-17-Driven Inflammatory Diseases." Case Western Reserve University School of Graduate Studies / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=case162673878106271.
Повний текст джерелаChitiprolu, Maneka. "Novel Regulatory Mechanisms of Autophagy in Human Disease: Implications for the Development of Therapeutic Strategies." Thesis, Université d'Ottawa / University of Ottawa, 2018. http://hdl.handle.net/10393/38441.
Повний текст джерелаDidillon, Andréanne. "RNA-Binding Protein HuD as a Potential Therapeutic Target for Spinal Muscular Atrophy." Thesis, Université d'Ottawa / University of Ottawa, 2018. http://hdl.handle.net/10393/37117.
Повний текст джерелаTordo, J. "Vectors for therapeutic antisense sequences delivery and the modification of messenger RNA processing." Thesis, University College London (University of London), 2013. http://discovery.ucl.ac.uk/1383711/.
Повний текст джерелаageely, Eman. "Chemical Tools for Potential Therapeutic Applications of CRISPR Systems." OpenSIUC, 2020. https://opensiuc.lib.siu.edu/dissertations/1831.
Повний текст джерелаMattis, Virginia B. "Molecular genetics of spinal muscular atrophy insights into various routes of therapeutic intervention /." Diss., Columbia, Mo. : University of Missouri-Columbia, 2009. http://hdl.handle.net/10355/6761.
Повний текст джерелаThe entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Vita. "May 2009" Includes bibliographical references.
Roura, Frigolé Helena. "Biomedical studies of human adenosine deaminase acting on transfer RNA and related therapeutic strategies." Doctoral thesis, Universitat de Barcelona, 2018. http://hdl.handle.net/10803/650900.
Повний текст джерелаL’adenosina deaminasa específica per RNA de transferència (ADAT) és un enzim humà heterodimèric que catalitza la reacció de deaminació de l’adenosina (A) a inosina (I) a la primera posició de l’anticodó de RNAs de transferència (tRNAs) (també anomenada posició 34 o posició de balanceig); una de les poques modificacions post-transcripcionals essencials en tRNAs (1-5). La inosina 34 permet el reconeixement de tres nucleòtids diferents: citidina, uridina i adenosina, a la tercera posició del codó, augmentant per tant la capacitat de descodificació dels tRNAs a més d’un codó en l’RNA missatger (mRNA) (l’adenosina 34 en principi únicament pot aparellar-se amb uridina en la tercera posició) (6, 7). Això altera els nivells de tRNAs disponibles per cada codó i s’ha demostrat que alinea la correlació entre l’ús de codons i número de còpies gèniques de cada tRNA (8). També s’ha suggerit que millora la fidelitat i eficiència de la traducció (8, 9), especialment per mRNAs enriquits en codons traduïts per tRNA modificats (10, 11). Monitoritzar la deaminació produïda per ADAT és clau per la caracterització de l’enzim en termes d’activitat, substrats, regulació, així com també pel disseny de fàrmacs. No obstant, aquest anàlisi és sovint complex, laboriós i poc quantitatiu. Per això, hem desenvolupat un assaig de deaminació in vitro basat en el polimorfisme de longitud dels fragments de restricció (RFLP) amb el propòsit de monitoritzar l’activitat d’ADAT de manera eficient, cost-efectiva i semiquantitativa (12). Per superar una limitació del mètode essent la necessitat de transcripció reversa i amplificació del tRNA, hem dissenyat un mètode directe per quantificar la formació d’I34 in vitro utilitzant els primers anàlegs fluorescents d’àcids nucleics que són substrats de deaminacions enzimàtiques descrits fins al moment (13-15). ADAT ha estat conservat en l’evolució amb l’adquisició de multi-especificitat de substrat. Mentre que el seu homòleg bacterià TadA deamina exclusivament tRNAArg (2), l’enzim humà deamina vuit tRNAs diferents (3, 16). Tot i així, els mecanismes que van conduir a aquesta evolució romanen desconeguts. Mentre que el reconeixement de substrat en TadA es coneix bé, en ADAT eucariòtic ha estat poc estudiat. A través d’assajos enzimàtics in vitro amb diferents variants de tRNAArg i tRNAAla, hem elucidat els trets més importants per a una conversió eficient d’A34 a I34 i hem caracteritzat el reconeixement de substrat per part de l’enzim humà. També proposem un nou potencial mecanisme de control de l’activitat d’ADAT per part de fragments derivats de tRNAs humans, el qual ofereix noves perspectives en la regulació de la funció d’ADAT i que pot obrir la porta al desenvolupament de noves estratègies per modular-ne l’activitat. Una mutació sense sentit (V128M) en una de les dues subunitats en l’enzim ADAT humà s’ha associat a retard mental i estrabisme, encara que les bases moleculars de la patologia es desconeixen (17, 18). Hem caracteritzat ADAT humà en termes de cinètica enzimàtica i estructura, i n’hem investigat l’efecte de la mutació V128M. Hem descobert que la substitució de valina 128 per metionina redueix l’activitat deaminatòria d’ADAT i que altera severament l’estabilitat de l’estructura quaternària de l’enzim. En aquest aspecte, hem descobert molècules amb l’habilitat d’activar l’enzim, la qual cosa podria revertir potencialment la reducció en l’activitat enzimàtica causada per la mutació. References 1. Gerber AP, Keller W. An adenosine deaminase that generates inosine at the wobble position of tRNAs. Science. 1999;286(5442):1146-9. Epub 1999/11/05. 2. Wolf J, Gerber AP, Keller W. tadA, an essential tRNA-specific adenosine deaminase from Escherichia coli. The EMBO journal. 2002;21(14):3841-51. Epub 2002/07/12. 3. Torres AG, Pineyro D, Rodriguez-Escriba M, Camacho N, Reina O, Saint-Leger A, et al. Inosine modifications in human tRNAs are incorporated at the precursor tRNA level. Nucleic acids research. 2015;43(10):5145-57. Epub 2015/04/29. 4. Zhou W, Karcher D, Bock R. Identification of enzymes for adenosine-to-inosine editing and discovery of cytidine-to-uridine editing in nucleus-encoded transfer RNAs of Arabidopsis. Plant physiology. 2014;166(4):1985-97. Epub 2014/10/16. 5. Tsutsumi S, Sugiura R, Ma Y, Tokuoka H, Ohta K, Ohte R, et al. Wobble inosine tRNA modification is essential to cell cycle progression in G(1)/S and G(2)/M transitions in fission yeast. J Biol Chem. 2007;282(46):33459-65. Epub 2007/09/19. 6. Crick FH. Codon--anticodon pairing: the wobble hypothesis. Journal of molecular biology. 1966;19(2):548-55. Epub 1966/08/01. 7. Torres AG, Pineyro D, Filonava L, Stracker TH, Batlle E, Ribas de Pouplana L. A-to-I editing on tRNAs: biochemical, biological and evolutionary implications. FEBS Lett. 2014;588(23):4279-86. Epub 2014/09/30. 8. Novoa EM, Pavon-Eternod M, Pan T, Ribas de Pouplana L. A role for tRNA modifications in genome structure and codon usage. Cell. 2012;149(1):202-13. Epub 2012/04/03. 9. Schaub M, Keller W. RNA editing by adenosine deaminases generates RNA and protein diversity. Biochimie. 2002;84(8):791-803. Epub 2002/11/30. 10. Rafels-Ybern A, Attolini CS, Ribas de Pouplana L. Distribution of ADAT-Dependent Codons in the Human Transcriptome. International journal of molecular sciences. 2015;16(8):17303- 14. Epub 2015/08/01. 11. Rafels-Ybern A, Torres AG, Grau-Bove X, Ruiz-Trillo I, de Pouplana LR. Codon adaptation to tRNAs with Inosine modification at position 34 is widespread among Eukaryotes and present in two Bacterial phyla. RNA biology. 2017:0. Epub 2017/09/08. 12. Wulff TF, Arguello RJ, Molina Jordan M, Roura Frigole H, Hauquier G, Filonava L, et al. Detection of a Subset of Posttranscriptional Transfer RNA Modifications in Vivo with a Restriction Fragment Length Polymorphism-Based Method. Biochemistry. 2017;56(31):4029-38. Epub 2017/07/14. 13. Sinkeldam RW, McCoy LS, Shin D, Tor Y. Enzymatic interconversion of isomorphic fluorescent nucleosides: adenosine deaminase transforms an adenosine analogue into an inosine analogue. Angew Chem Int Ed Engl. 2013;52(52):14026-30. Epub 2013/11/30. 14. McCoy LS, Shin D, Tor Y. Isomorphic emissive GTP surrogate facilitates initiation and elongation of in vitro transcription reactions. Journal of the American Chemical Society. 2014;136(43):15176-84. Epub 2014/09/26. 15. Rovira AR, Fin A, Tor Y. Chemical Mutagenesis of an Emissive RNA Alphabet. J Am Chem Soc. 2015;137(46):14602-5. Epub 2015/11/03. 16. Juhling F, Morl M, Hartmann RK, Sprinzl M, Stadler PF, Putz J. tRNAdb 2009: compilation of tRNA sequences and tRNA genes. Nucleic acids research. 2009;37(Database issue):D159-62. Epub 2008/10/30. 17. Alazami AM, Hijazi H, Al-Dosari MS, Shaheen R, Hashem A, Aldahmesh MA, et al. Mutation in ADAT3, encoding adenosine deaminase acting on transfer RNA, causes intellectual disability and strabismus. Journal of medical genetics. 2013;50(7):425-30. Epub 2013/04/27. 18. El-Hattab AW, Saleh MA, Hashem A, Al-Owain M, Asmari AA, Rabei H, et al. ADAT3- related intellectual disability: Further delineation of the phenotype. American journal of medical genetics Part A. 2016;170A(5):1142-7. Epub 2016/02/05.
Torres, Cabestany Pascual. "Cell Stress and RNA Splicing in Amyotrophic Lateral Sclerosis: Novel Opportunities for Therapeutic Development." Doctoral thesis, Universitat de Lleida, 2021. http://hdl.handle.net/10803/671440.
Повний текст джерелаLa ELA es una enfermedad neurodegenerativa multifactorial. Dado que actualmente es una enfermedad incurable sin una causa conocida, los esfuerzos para descubrir nuevas dianas terapéuticas están bien justificados. La evidencia disponible indica que la fisiopatología de la ELA puede estar compuesta parcialmente de interacciones entre alteraciones de lípidos, estrés oxidativo, deslocalización de TDP-43 y metabolismo del ARN. Para explorar el impacto de la deslocalización de TDP-43, cuantificamos por primera vez el splicing críptico derivado de la disfunción de TDP-43 en tejido humano, modelos celulares y ratones. Los exones crípticos son candidatos a biomarcadores en la ELA, y los cuantificamos en otras patologías relacionadas con alteraciones de TDP-43, como la demencia tipo Alzheimer-LATE. Uno de los ARNm controlados por TDP-43 codifica para ATG4B, una proteína esencial en la formación de la maquinaria de membrana de la autofagia. Por otro lado, las membranas del sistema nervioso central están enriquecidas en ácidos grasos poliinsaturados (PUFA), muy sensibles al estrés oxidativo. Las publicaciones anteriores del grupo demuestran una disminución en el ácido docosahexaenoico (DHA) -un PUFA- en la médula espinal de los donantes de ELA. El DHA es un regulador crucial de la inflamación y se ha relacionado con enfermedades neurodegenerativas relacionadas con la edad. Esta tesis muestra que la intervención dietética puede aumentar eficazmente el contenido de DHA de la médula espinal mediante el uso de una dieta enriquecida con DHA, que tiene un efecto beneficioso en la supervivencia de los ratones transgénicos machos. Esta mejora se asoció con una disminución de los marcadores inflamatorios y de daño del ADN. Debido a que se observa un daño en el ADN similar y un perfil de liberación de citocinas en el perfil secretor asociado a la senescencia (SASP) en la neuroinflamación, también examinamos el papel potencial de la senescencia en la ELA. Detectamos niveles aumentados de marcadores SASP y signos de senescencia celular (expresión aumentada de p16-INK y p21) en etapas presintomáticas y sintomáticas en la médula espinal de los ratones hSOD1-G93A. Sin embargo, el tratamiento senolítico con Navitoclax (un inhibidor de Bcl-2) no ofreció ningún beneficio en la supervivencia de los ratones ni una disminución de los niveles de expresión de genes de senescencia celular y marcadores SASP. También demostramos que el splicing críptico aumenta en ratones hSOD1-G93A en la etapa final y se correlaciona con el marcador de senescencia p16-INK. Por último, para mejorar el potencial de transferencia, exploramos las alteraciones del splicing críptico y cambios metabolómicos como potenciales biomarcadores periféricos. Desafortunadamente, los exones crípticos medidos en tejido nervioso no se expresan en células mononucleares de sangre periférica. No obstante, los análisis del metaboloma plaquetario revelaron cambios significativos en los enfoques de casos-controles y de pronóstico. En conclusión, esta tesis destaca los hallazgos novedosos relacionados con posibles intervenciones dietéticas y senolíticos, y propone nuevos biomarcadores metabolómicos y transcriptómicos.
ALS is a multifactorial neurodegenerative disease. As it is currently an incurable disease without a known cause, the efforts in discovering novel targets are well justified. Available evidence indicates that ALS pathophysiology can be partially comprised of interactions between lipid alterations, oxidative stress, TDP-43 mislocalization, and RNA metabolism. In order to explore the impact of TDP-43 mislocalization, we quantified for the first time the cryptic exon splicing derived from TDP-43 dysfunction in human tissue, cell models, and mice. Cryptic exons are candidate biomarkers in ALS, and we quantified them in other pathologies related to TDP-43 disturbances, such as the Alzheimer-LATE type dementia. One of the TDP-43 controlled mRNAs is codifying for ATG4B, an essential protein at the build-up of autophagy's membranal machinery. On the other hand, the central nervous system membranes are enriched in polyunsaturated fatty acids (PUFAs), which are very sensitive to oxidative stress. The group's previous publications indicated a decrease in docosahexaenoic acid (DHA) -a PUFA- in ALS donors' spinal cord. DHA is a crucial regulator of inflammation and has been implicated in age-related neurodegenerative diseases. This thesis shows that dietary intervention can effectively increase DHA content of the spinal cord by using a DHA enriched diet, which has a beneficial effect on male survival time. This improvement was associated with decreased inflammatory and DNA damage markers. Because a similar DNA damage and cytokine release profile are seen in senescence-associated secretory profile (SASP) in neuroinflammation, we also examined the potential role of senescence in ALS. We detected increased levels of SASP markers and signs of cell senescence (increased expression of p16-INK and p21) in pre- and symptomatic stages in the hSOD1-G93A ALS spinal cord. However, a senolytic treatment with Navitoclax (a Bcl-2 inhibitor) did not offer any benefit in mice survival nor a decreased level of cell senescence and SASP markers. We also demonstrate that cryptic exon splicing is increased in the hSOD1-G93A ALS model at the end-stage, and it is correlated with senescence marker p16-INK mRNA. Finally, to enhance transference potential, we explored both metabolomic and cryptic exon splicing alterations in peripheral biomarkers. Unfortunately, cryptic exons measured in nervous tissue are not expressed in peripheral blood mononuclear cells. Notwithstanding, platelet metabolome analyses revealed significant changes in case-control and prognostic approaches. Globally, this thesis highlights novel findings related to potential dietary interventions, open the door for new therapeutic agents such as senolytic and propose new metabolomics and transcriptomic biomarkers.
Hopkins, Tom. "The RNA-binding protein LARP1 as potential biomarker and therapeutic target in ovarian cancer." Thesis, Imperial College London, 2014. http://hdl.handle.net/10044/1/32144.
Повний текст джерелаThompson, Michael Ryan Haden. "An Evaluation of Host Factors as Novel Therapeutic Targets During Influenza Infection Using RNA Technologies." CSUSB ScholarWorks, 2018. https://scholarworks.lib.csusb.edu/etd/721.
Повний текст джерелаGiering, Jeffery C. "Development of a safe and effective polymerase II promoter-based short-hairpin RNA model therapeutic /." May be available electronically:, 2008. http://proquest.umi.com/login?COPT=REJTPTU1MTUmSU5UPTAmVkVSPTI=&clientId=12498.
Повний текст джерелаZhu, Meifen, and 朱玫芬. "Mir-23a involves in the anti-cancer effect of CRAE and berberine in human hepatocellular carcinoma cells." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B46944771.
Повний текст джерелаBradford, Seth Stephen. "The Design and Evaluation of Catalytic MetalloDrugs Targeting HCV IRES RNA: Demonstration of a New Therapeutic Approach." The Ohio State University, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=osu1345132549.
Повний текст джерелаPfeiffer, Isabell [Verfasser], and Lars [Akademischer Betreuer] Nitschke. "Generation of effective designer dendritic cells for therapeutic cancer vaccination using RNA electroporation / Isabell Pfeiffer. Gutachter: Lars Nitschke." Erlangen : Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 2013. http://d-nb.info/1075740398/34.
Повний текст джерелаHicks, Mellissa. "Signaling Networks as Possible Therapeutic Implications in Breast Cancer." The Ohio State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=osu1405945861.
Повний текст джерелаPfister, Edith L. "Therapeutic Silencing of Mutant Huntingtin by Targeting Single Nucleotide Polymorphisms: A Dissertation." eScholarship@UMMS, 2012. https://escholarship.umassmed.edu/gsbs_diss/618.
Повний текст джерелаSilva, Evangelista Cláudia. "Molecular Characterization of Pediatric Brainstem Gliomas (DIPG) and Identification of New Therapeutic Targets." Thesis, Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLS269.
Повний текст джерелаDIPG is one of the most severe paediatric brain tumours. No progress has been made in their management over the past 50 years and radiotherapy remains only transiently effective. Recently, a specific somatic mutation in the histone H3 (K27M) has been found in approximately 95% of DIPG patients and can be considered as the oncogenic driver of these tumours. Two major subgroup of patients with distinct oncogenic program and response to radiotherapy can be defined according to the gene in which the alteration occurs, encoding the H3.1 or H3.3 protein variants. We performed two synthetic lethality screens by RNA interference targeting the human kinome in order to identify the genes responsible for DIPG cell survival, as well as those sensitizing tumour cells to radiotherapy after inhibition. The dual purpose of this project was to better understand the biology underlying oncogenesis of DIPGs and to discover new therapeutic targets.We identified 41 genes required for DIPG cell survival with no major deleterious effect on normal control cells. Among them, we identified VRK3, a serine threonine kinase never involved in DIPG oncogenesis with functions remaining poorly described to date. We have shown that its inhibition leads to a complete arrest of DIPG cell proliferation and is additionally associated with important morphological changes, more particularly in H3.3-K27M mutated tumours. VRK3 is therefore a promising new therapeutic target for all patients in this fatal pathology.In parallel, a similar survival screen was performed in conjunction to cell radiation and very few interfering RNAs enhance H3.3-K27M cell radiosensitivity, in contrast to H3.1-K27M cells. These data highlighted a significant difference in radiosensitivity of the DMG in vitro models in H3.1- versus H3.3-K27M mutated tumours, in a concordant way with patient survival following radiotherapy. These unprecedented results suggest new opportunities for improving the current treatment of DIPG patients regardless of their genotype
Mahasha, Phetole Walter. "Compartmentalization, adaptive evolution and therapeutic response of HIV-1 in the gastrointestinal tract (GIT) of African patients infected with Subtype C: implications for the enhancement of therapeutic efficacy." Thesis, University of Pretoria, 2014. http://hdl.handle.net/2263/43156.
Повний текст джерелаThesis (PhD)--University of Pretoria, 2014.
lk2014
Immunology
PhD
Unrestricted
Sengal, Asmerom Tesfamariam. "Prognostic, predictive, and therapeutic role of FGFR2 isoforms and cognate FGF ligands in endometrial cancer." Thesis, Queensland University of Technology, 2020. https://eprints.qut.edu.au/205851/1/Asmerom%20Tesfamariam_Sengal_Thesis.pdf.
Повний текст джерелаBinzel, Daniel W. "Thermodynamics and Kinetics of the Three-Way Junction of Phi29 Motor pRNA and its Assembly into Nanoparticles for Therapeutic Delivery to Prostate Cancer." UKnowledge, 2016. http://uknowledge.uky.edu/pharmacy_etds/53.
Повний текст джерелаGuillemette, Shawna S. "Investigating Tumor Suppressors in the DNA Damage Response: Caretakers of the Genome and Biomarkers to Predict Therapeutic Response: A Dissertation." eScholarship@UMMS, 2014. https://escholarship.umassmed.edu/gsbs_diss/712.
Повний текст джерелаGuillemette, Shawna S. "Investigating Tumor Suppressors in the DNA Damage Response: Caretakers of the Genome and Biomarkers to Predict Therapeutic Response: A Dissertation." eScholarship@UMMS, 2004. http://escholarship.umassmed.edu/gsbs_diss/712.
Повний текст джерелаMatloka, Magdalena. "MBNL derivatives for therapeutic application in myotonic dystrophy." Electronic Thesis or Diss., Sorbonne université, 2019. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2019SORUS269.pdf.
Повний текст джерелаMyotonic dystrophy (DM) is an autosomal neuromuscular disease encompassing two distinct forms, type 1 (DM1) and type 2 (DM2), which are caused by abnormal microsatellite expansions of C(C)TG repeats in the 3’UTR of the DMPK and first intron of ZNF9 genes, respectively. Mutant RNAs carrying expanded repeats are retained in the nucleus as riboprotein aggregates that abnormally sequester MBNL splicing factors leading to alternative splicing misregulations associated with clinical symptoms. Although various therapeutic approaches for DM are under development, there is no effective therapy available so far. In this study, we designed a novel gene therapy strategy with the use of an engineered MBNL RNA-binding protein derivative that acts as a CUGexp-decoy to release sequestered endogenous MBNL factors and restore their proper functions. Expression of the decoy results in the correction of DM1-associated features in both in vitro and in vivo models of the disease. Subsequent optimization processes were applied to the engineered decoy and the most potent derivate that increases its functional capacity was selected for further therapeutic application. Additionally, we developed an autoregulatory system based on a splice-sensor strategy to control transgene product expression and provided a proof-of-concept of its efficacy in both in vitro and in vivo systems. In conclusion, my work establishes the potency of gene therapy treatment for DM and support the use of the decoy-based approach as an alternate or complementary therapeutic intervention for DM
Jeandard, Damien. "Import d'ARN dans les mitochondries de cellules humaines : identification à grande échelle et applications thérapeutiques." Thesis, Strasbourg, 2019. http://www.theses.fr/2019STRAJ005.
Повний текст джерелаMutations in the human mitochondrial genome are often associated with severe neuromuscular disorders. The first part of my thesis project consisted in the development of a therapeutic strategy based on the mitochondrial import of RNA molecules. I demonstrated that the stable expression of recombinant RNA molecules in human cells induced the decrease of the pathogenic mutation load in mitochondrial DNA. In the second part, I developed a nex method, CoLoC-seq, for the large-scale identification of RNA species localized in the mitochondria. By applying this method to human cells, I confirmed the mitochondrial targeting of some non-coding cytosolic RNAs and identified new potentially imported RNAs. These data will broaden the knowledge on the pathway of RNA targeting into the mitochondria, its mechanisms and regulation, and will allow optimization of the therapeutic strategies based on RNA import
Likhite, Shibi B. "Therapeutic suppression of mutant SOD1 by AAV9-mediated gene therapy approach in Amyotrophic Lateral Sclerosis." The Ohio State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=osu1417394084.
Повний текст джерелаVana, Karen. "The 37kDa/67kDa laminin receptor as a therapeutic target in prion diseases: potency of antisense LRP RNA, siRNAs specific for LRP mRNA and a LRP decoy mutant." Diss., lmu, 2006. http://nbn-resolving.de/urn:nbn:de:bvb:19-51200.
Повний текст джерелаBARONE, ELISA. "Overexpressed genes in malignant pleural mesothelioma: possible role in tumorigenesis and evaluation of their use as a prognostic marker." Doctoral thesis, Università di Siena, 2017. http://hdl.handle.net/11365/1005849.
Повний текст джерелаMadej, Roberta M. "The Impact of Imprecision in HCV Viral Load Test Results on Clinicians’ Therapeutic Management Decisions and on the Economic Value of the Test." VCU Scholars Compass, 2013. http://scholarscompass.vcu.edu/etd/3259.
Повний текст джерелаWoffindale, Caroline A. "RNA-based therapeutics for Alzheimer's disease." Thesis, University of Oxford, 2015. https://ora.ox.ac.uk/objects/uuid:8abb9f7b-9e49-4063-8395-83a57e9b14f7.
Повний текст джерелаDaniel, Rhonda W. "Dysregulation of microRNAs in Blood as Biomarkers for Diagnosing Prostate Cancer." VCU Scholars Compass, 2015. http://scholarscompass.vcu.edu/etd/3975.
Повний текст джерелаTonin, Yann. "Développement d'une stratégie thérapeutique anti-réplicative via l'exploitation de la voie d'import des ARN dans les mitochondries humaines." Thesis, Strasbourg, 2013. http://www.theses.fr/2013STRAJ093/document.
Повний текст джерелаMitochondria are involved in many metabolic pathways, and mutations in their genome (mtDNA) can cause a wide range of human disorders. No efficient treatment against these pathologies is currently available. The objective of this work consisted in the development of a therapeutic approach, called anti-replicative, based on the use of the natural pathway of RNA import into mitochondria. Small artificial RNA molecules able to be imported into human mitochondria have been used as vectors to address oligoribonucleotides capable to hybridize specifically to mutant mtDNA and to stop its replication. The effect of various chemical modifications on the stability, import and efficiency of these recombinant RNA has been characterized. All the data obtained prove the validity of the anti-replicative strategy for mtDNA containing a large deletion or pathogenic point mutations and can be considered as an important step to further develop an efficient therapy of mitochondrial diseases
Fernandes, Roberta Possato. "Quantificação do RNAm de tireoglobulina em sangue periférico de pacientes com câncer diferenciado de tireóide: acompanhamento a longo prazo." Universidade de São Paulo, 2009. http://www.teses.usp.br/teses/disponiveis/5/5135/tde-15042009-154717/.
Повний текст джерелаThe differentiated thyroid carcinoma (DTC) encloses 95% of all thyroid malignant disease. In USA, it increased 2,4 times in recent years (1973- 2002). The treatment includes total thyroidectomy, ablation with radioiodine (RAI) followed by TSH suppression with L-Thyroxine. The cancer recurrence occurs in 20% of the cases. Periodic evaluation through imaging examinations and serum thyroglobulin (TG) measurements by imunoassays method is recommended for careful follow-up of these patients. The anti-TG antibodies prevalence is 15-25% and would impair, partially, the serum TG use as a tumor marker. An alternative method to identify the recurrence of the tumor is the thyroid cells detection in peripheral blood, through the TG messenger RNA quantification (mRNA-TG) by real time RT-PCR. This new methodology increases the sensitivity detection for this molecule. The objective of this study was to verify the mRNA-TG peripheral blood quantification significance, as a complementary diagnostic method in the long term follow up of patients with DTC. Fourty five blood samples from patients with DTC have been collected before and 24, 48, 72 hours, 7 days, 1, 3, 6, 9 months, 1, 2, 4, 5, 6 and 7 years after the ablation therapy. Extensive technique standardization for mRNA-TG measurements was carried out to exclude methodological interventions and two housekeeping genes (GAPDH and HPRT1) were used to calculate the mRNA-TG concentrations. Concomitantly, serum TG measurements, hormonal profile and antibodies anti-TG assays were performed. The whole body scan was performed 7 days after RAI ablation to determine the stage of the disease. It was not possible to establish a cut-point value for mRNA-TG. The mRNA-TG did not differentiated the clinical stage of the disease in the long term follow-up and neither in the presence of anti-TG antibodies and TSH30ng/mL. Serum TG was able to differentiate the clinical stage of the patients during the follow-up. In conclusion mRNA-TG is not a good marker for the DCT recurrence, even when technical standardization, long term evaluation and the presence of antibodies anti-TG were considered. Thus it could not be used as a complementary diagnostic method in the DTC patients follow-up. This study confirmed the high sensivity of the real time RT-PCR whereas with very low specificity, consequently is unviable to be used in the DTC patients follow-up
Hatchell, Esme Claire. "Insight into estrogen action in breast cancer via the study of a novel nuclear receptor corepressor : SLIRP." University of Western Australia. School of Medicine and Pharmacology, 2008. http://theses.library.uwa.edu.au/adt-WU2008.0206.
Повний текст джерелаRen, Yin Ph D. Massachusetts Institute of Technology. "Tumor-penetrating delivery of small interfering RNA therapeutics." Thesis, Massachusetts Institute of Technology, 2012. http://hdl.handle.net/1721.1/72914.
Повний текст джерелаVita. Cataloged from PDF version of thesis.
Includes bibliographical references (p. 234-250).
Efforts to sequence cancer genomes have begun to uncover comprehensive lists of genes altered in cancer. Unfortunately, the number and complexity of identified alterations has made dissecting the underlying biology of cancer difficult, as many genes are not amenable to manipulation by small molecules or antibodies. RNA interference (RNAi) provides a direct way to assess and act on putative cancer targets. However, the translation of RNAi into the clinic has been thwarted by the "delivery" challenge, as small interfering RNA (siRNA) therapeutics must overcome clearance mechanisms and penetrate into tumor tissues to access cancer cells. This thesis sought to develop nanotechnology-based platforms to rapidly discover and validate cancer targets in vivo. First, we developed versatile surface chemistries for nanoparticle tumor targeting. Leveraging new discoveries in amplified transvascular transport, we designed a siRNA delivery system that integrates the tumor specificity and tissue-penetrating ability of tumor-penetrating peptides with membrane penetration properties of protein transduction domains to direct siRNA to tumors in vivo. Second, we utilized this delivery system to bridge the gap between cancer genomic discovery and in vivo target validation. Comprehensive analysis of ovarian cancer genomes identified candidate targets that are undruggable by traditional approaches. Tumor-penetrating delivery of siRNA against these genes potently impeded the growth of ovarian tumors in mice and improved survival, thereby credentialing their roles in tumor initiation and maintenance. Lastly, we described efforts extending this platform for clinical translation. Mechanistic studies identified functional properties that favored receptor-specific siRNA delivery. We also explored a strategy to improve the microdistribution of successively dosed siRNA therapeutics through modulating the tumor microenvironment. Finally, we investigated the utility of the system in primary human tumors derived from patients with ovarian cancer. Together, these findings illustrate that the combination of cancer genomics with the engineering of siRNA delivery nanomaterials establishes a platform for discovering genes amenable to RNAi therapies. As efforts in genome sequencing accelerate, this platform illustrates a path to clinical translation in humans.
by Yin Ren.
Ph.D.in Medical Engineering
Osborn, Maire. "Cellular RNA Targeting by Platinum (II) Anticancer Therapeutics." Thesis, University of Oregon, 2014. http://hdl.handle.net/1794/17920.
Повний текст джерелаChuanzheng, Zhou. "Conformationally Constrained Nucleic Acids as Potential RNA Targeting Therapeutics." Doctoral thesis, Uppsala universitet, Bioorganisk kemi, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-113680.
Повний текст джерелаMaeshima, Ruhina. "MYCN silencing as therapeutics for neuroblastoma using RNA interference." Thesis, University College London (University of London), 2018. http://discovery.ucl.ac.uk/10043849/.
Повний текст джерелаRoberts, Thomas C. "Duchenne muscular dystrophy : RNA-based therapeutics and microRNA biology." Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:f53ea1f3-92db-4f90-ba95-01f2a56eae8f.
Повний текст джерелаSutaria, Dhruvitkumar S. "INVESTIGATION OF DIFFERENTIALLY EXPRESSED NONCODING RNAS IN PANCREATIC DUCTAL ADENOCARCINOMA." The Ohio State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=osu1480550158159039.
Повний текст джерелаMazza, Rosangela Passos de Jesus. "Influência da infusão parenteral de aminoácidos sobre a expressão gênica de fatores de crescimento de timidina quinase no remanescente hepático de ratos desnutridos." Universidade de São Paulo, 2004. http://www.teses.usp.br/teses/disponiveis/5/5160/tde-15102014-090956/.
Повний текст джерелаGlutamine dipeptide (Gln) improve hepatic regeneration of nourished rats. To evaluate molecular effect of Gln on liver remnant 52 rats was classified into: 1. Nourished with partial hepatectomy (PH) and Gln (N-Gln=10) or proline (N-Pro=10); 2. Malnourished (MN) with PH: (MN-Gln=10) or (MN-Pro=10); 3. Nourished and Malnourished rat without PH (N-Control=6) and (MN-Control=6). Results: DNA = (MN-Gln, MN-Pro and MN-Control < N-Gln, N-Pro and N-control), (N-Gln, N-Pro, MN-Gln and MN-Pro < N and MN-Control), (N-Gln > MN-Gln); RNA= (N-Gln, N-Pro, MN-Gln and MN-Pro < N and MN-Control), (N-Gln > MN-Gln and N-Pro). There was no difference on transcript genes (TG) for HGF, TGF-a and thymidine kinase. Conclusions: Malnutrition and PH decrease hepatic DNA and RNA; Gln does not modify TG studied 96 hours after PH in MN rats
Thomas, Gregory Stuart. "Targeting prostate cancer with synthetic RNA ligands." Diss., University of Iowa, 2012. https://ir.uiowa.edu/etd/1508.
Повний текст джерелаDeng, Lin. "The role of non-coding RNA in the development of pulmonary arterial hypertension." Thesis, University of Glasgow, 2016. http://theses.gla.ac.uk/7828/.
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