Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 18 of 18 for “"RNA Therapeutics"”.
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RNA Therapeutics for Fibrolamellar Hepatocellular Carcinoma
… on the oncokinase I screened short hairpin RNAs (shRNAs) that tile over the fusion junction of the DNAJB1::PRKACA mRNA. I identified a shRNA that achieves strong knockdown of the fusion gene with minimal effect on the wildtype fusion partners.Using this shRNA, I demonstrate that specifically …
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Tumor-penetrating delivery of small interfering RNA therapeutics
… 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 …
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Development of Chemically-Defined Platform Materials for Localized Delivery of RNA Therapeutics
Most nucleic acid therapeutics have been engineered for systemic delivery with accumulation predominantly occurring in the liver. Currently, mRNA and siRNA represent the most clinically advanced nucleic acid modalities which can be used to address underlying under- or over-expression of crucial …
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DEVELOPMENT OF AN IN VIVO MULTITASKING BIOLUMINESCENT REPORTER GENE PLATFORM FOR THE PRECLINICAL EVALUATION OF RNA THERAPEUTICS
RNA-based therapeutics have emerged as a transformative class of medicines, enabling precise modulation of gene expression through sequence-defined mechanisms and offering novel therapeutic opportunities for previously intractable diseases. The potential of these drugs to address unmet …
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miR-10b Rescues Diabetes and GI Dysmotility Associated with a Leaky Gut
… pharmaceutical development. Current advances in RNA-based therapies have substantial promise in treating and preventing many human diseases and disorders through fixing the pathology instead of merely treating the symptomology, like traditional therapeutics. Although many RNA therapeutics have …
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RNA-level controllers for programmable gene expression in mammalian cells
… Here, through two examples, we demonstrate that RNA is well-suited for engineering compact, programmable biomolecular tools with sense and actuate functionalities. In the first half of this thesis, we develop a microRNA-based strategy to precisely overwrite the expression level of an endogenous …
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Developing in vitro models to elucidate the mechanisms of toxicity of locked nucleic acid gapmer antisense oligonucleotides.
… oligonucleotides are an emerging class of RNA therapeutics that have recently received several approvals from the clinic. Antisense oligonucleotides act at the RNA level to either degrade target RNA, or to regulate splicing of a particular gene, and have been applied to treat a variety of …
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Advancing and expanding siRNA and saRNA therapeutics applications through chemical modifications
Oligonucleotides are short strands of DNA or RNA that are used to treat complex diseases like cancer and rare genetic diseases. They rely on biological pathways in our body to work. Two pathways that are important to this study are gene silencing and activation. Short interfering RNAs (siRNAs) …
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Characterization of the Dimerization and Salt Dependent Aggregation of the ALS-Linked Protein TDP-43
… DNA-binding protein 43 (TDP-43) is essential for RNA processing but can also form toxic cytoplasmic inclusions in neurons of patients with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). RNA-binding has been shown to have the potential to decrease or inhibit the …
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Development and mechanistic analysis of in vivo liposomal nanoparticle delivery of siRNA and mRNA
A limited number of siRNA and mRNA based therapeutics have been developed largely due to the difficulties of efficaciously delivering RNA to cells in vivo. Liposomal nanoparticles (LNPs) have shown some success, but their design is limited by both a lack of information concerning the optimal lipid …
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Design, Off-Target Toxicity, and Intracellular Processing of Nucleotide-Modified Messenger RNAs for Human Therapies
RNA therapy is a modality, analogous to gene therapy, in which in vitro-transcribed mRNA (IVT mRNA) is introduced to cells for therapeutic applications. IVT mRNA is transfected into target cells, translated, and the fully-synthesised encoded protein exerts a therapeutic effect via specific …
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Analysis of Protein and RNA Interactions of the HIV-1 rev Protein
… nucleus via it’s nuclear localization sequence/RNA binding domain and interacts with a ≈234 nt region of viral RNA, termed the Rev Response Element (RRE), which is located in the <em>env</em> region of unspliced and singly-spliced HIV-1 mRNA. The Rev nuclear export sequence (NES) then mediates …
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The Design, Synthesis, and Evaluation of Zwitterionic and Cationic Lipids for In Vivo RNA Delivery and Non-Viral CRISPR/Cas Gene Editing
… treatment of many genetic diseases. The use of RNA interference (RNAi) as a therapeutic is an exciting and rapidly developing field that offers a promising alternative to small molecule drugs for the treatment of dysregulatory diseases, including cancer. Small interfering RNA (siRNA) can be …
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The role of long non-coding RNA LINC00673 in lung tumorigenesis
… involving multiple cellular species. Non-coding RNAs (ncRNAs) are a class of RNA molecules varying in size, biogenesis and mechanism of action that have established themselves as key regulators of cellular behaviour. This project explores the roles of long non-coding RNA (lncRNA) in the …
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The Interrogation of Cas9 Aptamers and sgRNA Structures Through SELEX
… of Cas9, the interrogation and evolution of sgRNA scaffold, in addition to novel Cas9 binding RNAs, represent another echelon of development and therapeutic potential. Currently, the majority of research utilizes a singular guide RNA scaffold sequence (the sgRNA) for a given Cas protein (e.g., …
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Characterization of A Novel Oncogenic Mirna Inhibitor In Cancer Therapy
… thought to be undruggable regions of the genome, RNA has become an area of increasing interest in cancer due to the identification of more targetable regions and their relationship to tumor growth and progression. This work reports on the development of IACS-13743, a novel small molecule found to …
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Single-Molecule Characterization of RNA via Nanopore Sensing
Precise characterization of RNA is essential for understanding a wide range of biological processes, studying gene expression, developing new RNA-based therapeutic technologies, and elucidating disease mechanisms. However, current RNA characterization methods often provide an incomplete picture of …
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DEVELOPMENT OF VIRTUAL SCREENING METHODOLOGIES FOR IDENTIFYING RNA-BASED THERAPIES
… methodologies for predicting protein-RNA binding affinities and designing RNA sequences with specific functional outcomes. The research introduces PANTHER (Protein-Affinity for Nucleic Target-binding, Hybridization, and Energy Regression), a novel machine learning-based scoring …