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 20 of 130 for “"AAV"”.
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Cross-Species Evolution of New AAV Variants
… and tissues. Recombinant adeno-associated viral (AAV) vectors are a promising delivery platform, but ongoing clinical trials continue to highlight a relatively narrow therapeutic window. Efforts to optimize vector dosing or engineer improved vectors are confounded, at least in part, by differences …
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LIVER FIBROSIS IMPAIRS HEPATOCYTE TRANSDUCTION BY AAV VECTORS
Adeno-associated viral vectors (AAVs) are the most promising tools for liver directed gene therapy. However, integrity of hepatic architecture has been considered pre-requisite for efficient gene delivery and clinical studies have been addressed toward patients with no or negligible hepatic damage …
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The Genetics of Anti-Neutrophil Cytoplasmic Antibody Associated Vasculitis (AAV)
… antibody (ANCA)-associated vasculitis (AAV) is a multi-systemic autoimmune disorder with evidence of circulating pathogenic ANCA. There are two main antigenic targets: proteinase 3 (PR3) and myeloperoxidase (MPO). Previous genome-wide association studies (GWAS) have provided evidence …
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Immune responses to AAV gene therapy in the ocular compartment
Adeno-associated virus (AAV) is a viral vector that can be used to deliver therapeutic genes to diseased cells in the eye. Whilst some consider the eye to be an immuneprivileged organ, recent reports have begun to suggest that injection of AAV may elicit local and systemic immune activation. The …
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Analysis, Optimization and Application of AAV Capsid Assembly using Escherichia coli
Recombinant adeno-associated viruses (rAAV) are leading drugs in gene therapy with three products approved by the European Medicines Agency (EMA) and the Food and Drug Administration (FDA). Currently, rAAV vectors are evaluated in many ongoing clinical trials for treating rare genetic diseases and …
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MUTAGENESIS OF AAV CAPSID PROTEINS FOR ENHANCED TRANSDUCTION OF CARDIAC CELL TYPES
Background: Adeno- associated virus serotype 9 (AAV9) has a high transduction efficiency for cardiac tissues, along with liver, skeletal muscle, pancreatic tissue, and the eye, versus other AAV serotypes. Unfortunately, nonspecific targeting to the intended tissue can result in the need for use of …
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Improving the Safety and Efficacy of AAV Gene Therapy for Hemophilia A
… long-term efficacy after adeno-associated viral (AAV) vector delivery of the F8 gene to hepatocytes. To address questions of safety, we treated privately owned dogs with a liver directed AAV serotype 8 vector encapsidating a canine F8 gene. These dogs were followed long-term for efficacy of the …
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PIECING TOGETHER THE PUZZLE OF TREATING HEMOPHILIA A UTILIZING AAV BASED GENE THERAPY
… being studied for use in gene therapy is AAV. AAV is a small virus, which is relatively easily augmented to produce replication deficient therapeutic agents. While AAV looks to be a potential solution to the delivery aspect of gene therapy, there are still many issues with AAV use. AAV is …
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Cationic liposome-mediated transfection of mammary epithelial cells with AAV-based plasmid DNA
… delivery of adeno-associated virus (AAV) based plasmid DNA has potential for efficient and safe delivery of DNA into a number of different cell types. The objective of this thesis was to develop techniques for transfecting adult somatic mammary epithelial cells with the aim of …
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Production of AAV vectors for gene therapy : a cost-effectiveness and risk assessment
… documenting the different existing processes for AAV production and developing a competitive analysis using information from ongoing clinical trials in the industry pipeline. The following process design steps were followed in order to fulfill the project objectives: (1) Define product …
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ADVANCED AAV-MEDIATED LIVER-DIRECTED GENE THERAPIES FOR HAEMOPHILIA A AND MUCOPOLYSACCHARIDOSIS TYPE VI
… gene therapy using adeno-associated viral (AAV) vectors holds significant promise for providing long-term transgene expression following a single systhemic administration. However, both the limited cargo capacity (~4.7 kb) and the non-integrative nature of AAV vectors prevent their …
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Pre-Clinical Development Of Aav Mediated Gene Therapy For Familial Lecithin Cholesterol Acyltransferase Deficiency
… with this disease. FLD is a good candidate for AAV mediated gene therapy but this therapeutic avenue has not been pursued until now. Here, we completed dose response studies in LCAT KO and LCAT KO/ human ApoA-I transgenic mice using AAV8 expressing human LCAT. AAV8-TBG-hLCAT induces significant …
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Developing an astrocyte-selective AAV-ADAMTS4 gene therapy to promote repair after spinal cord injury
… therapeutic molecules. Adeno-associated viral (AAV) vector gene therapy, in particular, has emerged as the vector of choice for safe, robust and long-term transgene expression in the central nervous system (CNS). Since astrocytes play an important role in SCI pathology, the first objective of …
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Non-motor symptoms in the aav-α-synuclein rat model of Parkinson’s disease: exercise as a therapeutic intervention
… impact of preclinical research. The AAV-α-synuclein rat model is the only animal model to date that has been shown to robustly and consistently reproduce the primary neuropathological and behavioural features of PD. However, there has been little research on the ability of the model …
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Systemic AAV-Mediated Gene Therapy Using Epo-R76E to Protect Retinal Ganglion Cells from Optic Nerve Injury and Disease
… study uses recombinant adeno-associated virus (rAAV) gene therapy and systemic delivery of EPO‑R76E to assess treatment potential for degenerating neurons in an induced model of neurodegeneration and a spontaneous model of glaucoma.</p> <p>Optic nerve crush is a model of retinal ganglion cell …
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CHARACTERIZATION OF THE AAV-PHP.B CAPSID AND ITS INTERACTION WITH THE LY6A RECEPTOR: IMPLICATIONS FOR RECEPTOR-TARGETED VECTOR ENGINEERING
… in murine models, the adeno-associated virus (AAV) vector AAV-PHP.B has demonstrated an ability to overcome this barrier and elicit robust transgene expression throughout the CNS when administered intravenously. AAV-PHP.B achieves this through an engineered receptor interaction with Ly6a, a …
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Phenotypic characterisation of the tremor mutant and AAV mediated aspartoacylase gene transfer in the rat model of Canavan disease
The doctoral studies described in this thesis involve the phenotypic characterization of the tremor rat, an animal model of Canavan disease, and a proof of principle gene transfer study in this model. The phenotype of the tremor rat is examined at the genetic, molecular, cellular, neurochemical, …
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OPTIMIZING GENE THERAPY: THE IMPACT OF SMALL MOLECULE MODULATORS ON ADENO-ASSOCIATED VECTOR TRANSDUCTION AND INTEGRATION
Adeno-associated virus (AAV) is a widely used vehicle for gene delivery but a limitation to AAV gene therapy can be inefficient transgene expression from AAV vectors. One approach to improve AAV transduction has been to combine the vector with small molecule modulators that disrupt cellular …
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Developing Adeno-Associated Viral Vectors As A Gene Editing Platform
The success of adeno-associated viral (AAV) vectors for gene replacement applications has spurred interest to repurpose AAV into a platform for CRISPR/Cas9 gene editing. Yet, AAV vector behaviors that are critical for gene editing have been unexplored. To safely and effectively combine AAV and …
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