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dc.contributor.advisorHughes, Stephanie
dc.contributor.authorCheong, Isaiah
dc.date.available2016-03-18T03:19:34Z
dc.date.copyright2016
dc.identifier.citationCheong, I. (2016). Gene therapy for Alzheimer’s disease: Characterising lentivirus and adeno-associated virus spread from the adult mouse hippocampus (Thesis, Master of Science). University of Otago. Retrieved from http://hdl.handle.net/10523/6288en
dc.identifier.urihttp://hdl.handle.net/10523/6288
dc.description.abstractAlzheimer’s Disease is a neurodegenerative condition with progressively worsening memory and cognitive function, which ultimately results in death. The two major neuropathological hallmarks of AD are extracellular amyloid-beta (Aβ) plaques and intracellular neurofibrillary tau tangles (NFTs). Other pathways and neuronal mechanisms are also likely to be affected as AD is a complex disease resulting from anomalies in components of different pathways. Currently, apart from a few FDA approved drugs which serve to delay symptom progression through slowing neurotransmitter breakdown (Cholinesterase inhibitors) and cell damage (NMDA-receptor antagonist), no effective treatment of the underlying causes of AD is available. One of the hypothesised underlying cause of AD is the formation of extracellular Aβ plaques. Current work in the Neural Development and Disease (NDD) lab have researched viral-mediated gene therapy as a means to introduce a neuroprotective secreted amyloid precursor protein α (sAPPα) gene intracranially. This project’s primary aim was optimising and comparing the spread between lentiviral (LV) and adeno-associated viral (AAV) vectors; along with the effects of systemically delivering an osmotic agent, mannitol. Viral spread would be determined by the use of a GFP reporter gene, where expression indicated transduction and extent of viral spread. This project has showed a significant improvement in transduction efficiency when using an AAV vector to deliver a reporter gene. It efficiently achieved widespread transduction of the CNS from a unilateral injection at the hippocampus. However, while LV had a limited spread in comparison to AAV9, it would be useful for targeted delivery of treatment. Mannitol did not produce any significant effect on vector spread. The secondary aim was to create a plasmid to visualise secretion of sAPPα from virally transduced cells. Once packaged into a lentiviral vector, the plasmid was shown to successfully transduce primary neurons in vitro, but expression of reporter genes were not observed in vivo.
dc.format.mimetypeapplication/pdf
dc.language.isoen
dc.publisherUniversity of Otago
dc.rightsAll items in OUR Archive are provided for private study and research purposes and are protected by copyright with all rights reserved unless otherwise indicated.
dc.subjectAlzheimer's Disease
dc.subjectGene therapy
dc.subjectViral vector
dc.subjectlentivirus
dc.subjectadeno-associated virus
dc.subjectsAPPα
dc.subjectmannitol
dc.titleGene therapy for Alzheimer's disease: Characterising lentivirus and adeno-associated virus spread from the adult mouse hippocampus
dc.typeThesis
dc.date.updated2016-03-17T23:08:01Z
dc.language.rfc3066en
thesis.degree.disciplineBiochemistry
thesis.degree.nameMaster of Science
thesis.degree.grantorUniversity of Otago
thesis.degree.levelMasters
otago.openaccessOpen
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