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 20 for “"AAV9"”.
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Correction of AB Variant GM2 Gangliosidoses Using AAV9 Viral Vector Gene Therapy in a Mouse Model
… a one-time treatment of single stranded (ss) AAV9/GM2A viral vector therapy at a dose of 1 x 1014 vector genomes per kilogram of mouse and to see at least biochemical reduction in GM2 ganglioside storage in both the short- and long-term treated cohorts. ssAAV9/GM2A plasmid was created and …
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OPTIMIZATION OF AAV9 GENE THERAPY FOR SPINAL MUSCULAR ATROPHY WITH RESPIRATORY DISTRESS TYPE 1 USING IN VIVO DISEASE MODELS
… of two adeno‐associated virus serotype 9 (AAV9)-IGHMBP2 vectors, carrying different promoters, by administering them intracerebroventricularly in SMARD1 mice model (nmd), during the presymptomatic phase of the disease at postnatal day 1. This comparison allowed us to determine which is the …
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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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AAV9-mediated (Pro)renin Receptor Antagonism Reduces High Fat Diet Induced Hyperglycemia and Hepatic Steatosis in Mouse Model of Non-alcoholic Fatty Liver Disease
… delivered by adeno-associated virus, serotype 9 (AAV9) vector via systemic route, based on the findings of a prior experiment in this study. Here we validated AAV-PHP.eB and AAV9 in Neuro-2A cells, and confirmed AAV-PHP.eB and AAV9 expression in the brain and in non-CNS tissues. In addition, we …
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IN VIVO AND IN VITRO EVALUATION OF THE COMBINATION OF RNA INTERFERING AND GENE THERAPY FOR TREATING MITOFUSIN2-RELATED DISEASES
… (CSF) delivery using adeno-associated virus 9 (AAV9). Results: We demonstrated the correct silencing of endogenous MFN2 and replacement with an exogenous copy of the functional wild-type gene in cells. This approach significantly rescues the CMT2A MN phenotype in vitro, stabilizing the altered …
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CHARACTERIZATION OF THE AAV-PHP.B CAPSID AND ITS INTERACTION WITH THE LY6A RECEPTOR: IMPLICATIONS FOR RECEPTOR-TARGETED VECTOR ENGINEERING
… graft the Ly6a binding epitope from its native AAV9 context into an AAV1 backbone and test the performance of the engineered variants in vivo. We then comprehensively explore the impact of receptor affinity on the systemic targeting and endothelial penetration properties of AAV vectors, using a …
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MODELLING RIBOFLAVIN TRANSPORTER DEFICIENCY (RTD) USING IPSC-DERIVED MODELS TO TEST GENE THERAPY EFFICACY
… using an adeno-associated viral vector 2/9 (AAV9) carrying the human codon optimized SLC52A2 cDNA. We optimized the in vitro transduction of motoneurons using Sialidase treatment. Our results proved that treated RTD motoneurons showed a significant increase in neurites’ length when compared …
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Cross-Species Evolution of New AAV Variants
… attributes benchmarked against AAV serotype 9 (AAV9). Increased potency of AAV.cc47 is evidenced through robust reporter gene expression as well as Cre-mediated recombination and CRISPR/Cas9-mediated genome editing in a fluorescent reporter mouse model. Enhanced transduction efficiency of …
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Expanding the toolkit of protease activatable viruses to improve their versatility and modularity
… for cardiac disease applications. These AAV9-based PAVs have been characterized in vitro, and the activatability of these PAVs ranges from 2.5x to 5.4x differences between the “locked” vs. “unlocked” states. The PAVs have also been characterized in vivo in a murine MI model. Compared to …
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Medical Engineering and Medical Physics: Metagenomic Sequencing for Viral Diagnostics and Discovery
… specific amino acids on the viral capsid of AAV9 and use sequencing to screen millions of viral capsid variants to evolve an engineered AAV with up to 100 times higher muscle tissue specificity over natural AAV.
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Identification and Characterization of MicroRNAs Modulating Cardiac Hypertrophy
… (TAC) in 8 weeks old CD1 mice (n=14 per group), AAV9-mediated delivery of miR-665 showed remarkable capacity to protect against pathological cardiac hypertrophy and preserve function over time. This effect was observed when the vectors were delivered either before (LVEF at 60 day after TAC: 51.3% …
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Identification and Characterization of the Role of REEP5 in Sarco-Endoplasmic Reticulum Formation, Maintenance, and Function in Cardiac Muscle
… Similarly, in vivo adeno-associated viral (AAV9)-induced REEP5 depletion in the mouse resulted in lethal diastolic cardiac dysfunction with dilated cardiac chambers and reduced ejection fraction. Altogether, these results demonstrated 1. Our cardiomyocyte membrane proteome dataset proves …
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Investigating the Effects of C9orf72 Haploinsufficiency on TDP-43 Pathology in ALS
… of TDP-43 proteinopathy was generated using AAV9-mediated intracerebroventricular (i.c.v) injections of EGFP-tagged pathological isoforms of TDP-43, TDP-35 and TDP-25. TDP-35 and TDP-25 mice exhibited differential expression patterns and behavioral deficits, with TDP-35 mice displaying …
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Developing an astrocyte-selective AAV-ADAMTS4 gene therapy to promote repair after spinal cord injury
… into the astrocyte tropic AAV serotypes: AAV5, AAV9, and AAVRec2. In cell culture and slice culture experiments, AAV5 was superior in terms of transduction efficiency, transgene expression, and astrocyte selectivity. Due to the packaging constraints of AAV vectors, an additional AAV5 vector was …
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THE ROLE OF CIRCULAR RNA CDR1AS IN MACROPHAGE MEDIATED CARDIAC INJURY AND REPAIR
… We performed tail vein injections of circ-cdr1as-AAV9 vectors 14 days prior to MI and conducted physiological and histological studies. Administration of circ-cdr1as-AAV9 significantly improved post-MI LV functions including ejection fraction (%EF) and fractional shortening (%FS) at 21-28D post …
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Novel mechanisms of diastolic dysfunction in diabetes
… intervention could rescue cardiac function, an AAV9 Gabarapl1- expressing virus was used to achieve cardiac-specific Gabarapl1 upregulation in a type 2 diabetic (T2D) model induced by high fat/sugar diet feeding. Key findings: (1) Molecular discovery: The diabetic heart is characterised by …
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Synaptic morphology, function, and regulation in a paediatric-onset neurodegenerative disorder
… degeneration can be prevented by administering AAV9-based gene therapy prior to symptom-onset. The hypothesis was that changes in synaptic morphology and function underlie cognitive decline in MPS IIIA. The aim of the study was to increase understanding of neurological dysfunction in MPS IIIA, …
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Molecular Mechanisms of Presynaptic Plasticity and Function in the Mammalian Brain
… and Syt7 were bicistronically expressed via AAV9 virus in CFs. This ectopic Syt7 expression in CFs led to big increases in low-Ca$_{ext}$ CF-PC facilitation, more than doubling PPF and more than tripling TF. While overexpression of Syt7 might turn out to have an effect on the initial release …
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Investigating modifiers that can regulate selective vulnerability in mouse models of spinal muscular atrophy
… subsequently PACAP was administered via AAV9 delivery in the Smn²ᴮ/⁻ mouse model, showing no significant effects on the neuropathology in the Smn²ᴮ/⁻ mouse model. Finally, since I have identified significant divergence in relative vulnerability in the neurons of the facial motor nucleus, …
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A STICKY SITUATION: ESSENTIAL ROLES OF ADHESION G PROTEIN COUPLED RECEPTORS ADGRF5 AND ADGRG1 IN CARDIAC HOMEOSTASIS AND FAILURE
… of ADGRF5-CTF to myocytes specifically via AAV9-cTnT-ADGRF5-CTF-Flag vs LacZ delivery, injected retro-orbitally 3-weeks post TAC-induction, revealed that ADGRF5 prevented the onset of cardiac failure in wild type mice. Taken together, this study reveals that ADGRF5 maintains cardiac …